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The influence of bio-behavioural factors on tumour biology: pathways and mechanisms

Abstract

Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.

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Figure 1: Important components of the central and peripheral stress systems.
Figure 2: Effects of stress-associated factors on the tumour microenvironment.
Figure 3: Integrated model of bio-behavioural influences on cancer pathogenesis through neuroendocrine pathways.

References

  1. 1

    Stefanek, M. & McDonald, P. G. in Handbook of Behavioral Science and Cancer (eds Miller, S. M., Bowen, D. J., Croyle, R. T. & Rowland, J.) (American Psychological Association, Washington DC) (in the press).

  2. 2

    Reiche, E. M., Nunes, S. O. & Morimoto, H. K. Stress, depression, the immune system, and cancer. Lancet Oncol. 5, 617–625 (2004).

    CAS  PubMed  Google Scholar 

  3. 3

    Spiegel, D. & Giese-Davis, J. Depression and cancer: mechanisms and disease progression. Biol. Psychiatry 54, 269–282 (2003).

    PubMed  Google Scholar 

  4. 4

    Price, M. A. et al. The role of psychosocial factors in the development of breast carcinoma: part I. The cancer prone personality. Cancer 91, 679–685 (2001).

    CAS  PubMed  Google Scholar 

  5. 5

    Lillberg, K. et al. Stressful life events and risk of breast cancer in 10,808 women: a cohort study. Am. J. Epidemiol. 157, 415–423 (2003).

    PubMed  Google Scholar 

  6. 6

    Glaser, R. & Kiecolt-Glaser, J. K. Stress-induced immune dysfunction: implications for health. Nature Rev. Immunol. 5, 243–251 (2005).

    CAS  Google Scholar 

  7. 7

    Chrousos, G. P. & Gold, P. W. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 267, 1244–1252 (1992).

    CAS  PubMed  Google Scholar 

  8. 8

    Charmandari, E., Tsigos, C. & Chrousos, G. P. Endocrinology of the stress response. Annu. Rev. Physiol. 67, 259–284 (2005).

    CAS  PubMed  Google Scholar 

  9. 9

    McEwen, B. S. Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology 22, 108–124 (2000).

    CAS  PubMed  Google Scholar 

  10. 10

    Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F. & Glaser, R. Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology. Annu. Rev. Psychol. 53, 83–107 (2002).

    PubMed  Google Scholar 

  11. 11

    McEwen, B. S. Sex, stress and the hippocampus: allostasis, allostatic load and the aging process. Neurobiol. Aging 23, 921–939 (2002).

    CAS  PubMed  Google Scholar 

  12. 12

    Sood, A. K. et al. Stress hormone mediated invasion of ovarian cancer cells. Clin. Cancer Res. 12, 369–375 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13

    Badino, G. R., Novelli, A., Girardi, C. & Di Carlo, F. Evidence for functional β-adrenoceptor subtypes in CG-5 breast cancer cell. Pharm. Res. 33, 255–260 (1996).

    CAS  Google Scholar 

  14. 14

    Vandewalle, B., Revillion, F. & Lefebvre, J. Functional β-adrenergic receptors in breast cancer cells. J. Cancer Res. Clin. Oncol. 116, 303–306 (1990).

    CAS  PubMed  Google Scholar 

  15. 15

    Marchetti, B., Spinola, P. G., Pelletier, G. & Labrie, F. A potential role for catecholamines in the development and progression of carcinogen-induced mammary tumors: hormonal control of β-adrenergic receptors and correlation with tumor growth. J. Steroid Biochem. Mol. Biol. 38, 307–320 (1991).

    CAS  PubMed  Google Scholar 

  16. 16

    Penninx, B. W. et al. Chronically depressed mood and cancer risk in older persons. J. Natl Cancer Inst. 90, 1888–1893 (1998).

    CAS  PubMed  Google Scholar 

  17. 17

    Reynolds, P. & Kaplan, G. A. Social connections and risk for cancer: prospective evidence from the Alameda County Study. Behav. Med. 16, 101–110 (1990).

    CAS  PubMed  Google Scholar 

  18. 18

    Allison, P. J., Guichard, C., Fung, K. & Gilain, L. Dispositional optimism predicts survival status 1 year after diagnosis in head and neck cancer patients. J. Clin. Oncol. 21, 543–548 (2003).

    PubMed  Google Scholar 

  19. 19

    Gotay, C. C. Behavior and cancer prevention. J. Clin. Oncol. 23, 301–310 (2005).

    PubMed  Google Scholar 

  20. 20

    Laconi, E. et al. Early exposure to restraint stress enhances chemical carcinogenesis in rat liver. Cancer Lett. 161, 215–220 (2000).

    CAS  PubMed  Google Scholar 

  21. 21

    Ben-Eliyahu, S., Yirmiya, R., Liebeskind, J. C., Taylor, A. N. & Gale, R. P. Stress increases metastatic spread of a mammary tumor in rats: evidence for mediation by the immune system. Brain Behav. Immun. 5, 193–205 (1991).

    CAS  PubMed  Google Scholar 

  22. 22

    Ben-Eliyahu, S., Page, G. G., Yirmiya, R. & Shakhar, G. Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int. J. Cancer 80, 880–888 (1999).

    CAS  PubMed  Google Scholar 

  23. 23

    Page, G. G. & Ben-Eliyahu, S. A role for NK cells in greater susceptibility of young rats to metastatic formation. Dev. Comp. Immunol. 23, 87–96 (1999).

    CAS  PubMed  Google Scholar 

  24. 24

    Page, G. G., Ben-Eliyahu, S., Yirmiya, R. & Liebeskind, J. C. Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain 54, 21–28 (1993).

    CAS  PubMed  Google Scholar 

  25. 25

    Stefanski, V. & Ben-Eliyahu, S. Social confrontation and tumor metastasis in rats: defeat and β-adrenergic mechanisms. Physiol. Behav. 60, 277–282 (1996).

    CAS  PubMed  Google Scholar 

  26. 26

    Ben-Eliyahu, S. et al. The NMDA receptor antagonist MK-801 blocks nonopioid stress induced analgesia and decreases tumor metastasis in the rat. Proc. West. Pharmacol. Soc. 36, 293–298 (1993).

    CAS  PubMed  Google Scholar 

  27. 27

    Melamed, R. et al. Marginating pulmonary-NK activity and resistance to experimental tumor metastasis: suppression by surgery and the prophylactic use of a β-adrenergic antagonist and a prostaglandin synthesis inhibitor. Brain Behav. Immun. 19, 114–126 (2005).

    CAS  PubMed  Google Scholar 

  28. 28

    Fischman, H. K., Pero, R. W. & Kelly, D. D. Psychogenic stress induces chromosomal and DNA damage. Int. J. Neurosci. 84, 219–227 (1996).

    CAS  PubMed  Google Scholar 

  29. 29

    Sacharczuk, M., Jaszczak, K. & Sadowski, B. Chromosomal NOR activity in mice selected for high and low swim stress-induced analgesia. Behav. Genet. 33, 435–441 (2003).

    PubMed  Google Scholar 

  30. 30

    Thaker, P. H. et al. in The 36th Annual Meeting of the Society of Gynecologic Oncologists 30 (Miami, Florida, 2005).

    Google Scholar 

  31. 31

    Ferrara, N. & Davis-Smyth, T. The biology of vascular endothelial growth factor. Endocr. Rev. 18, 4–25 (1997).

    CAS  PubMed  Google Scholar 

  32. 32

    Ohm, J. E. et al. VEGF inhibits T-cell development and may contribute to tumor-induced immune suppression. Blood 101, 4878–4886 (2003).

    CAS  PubMed  Google Scholar 

  33. 33

    Gabrilovich, D. I. et al. Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nature Med. 2, 1096–1103 (1996).

    CAS  PubMed  Google Scholar 

  34. 34

    Lutgendorf, S. K. et al. Vascular endothelial growth factor and social support in patients with ovarian carcinoma. Cancer 95, 808–815 (2002).

    CAS  PubMed  Google Scholar 

  35. 35

    Costanzo, E. S. et al. Psychosocial factors and interleukin-6 among women with advanced ovarian cancer. Cancer 104, 305–313 (2005).

    PubMed  Google Scholar 

  36. 36

    Fredriksson, J. M., Lindquist, J. M., Bronnikov, G. E. & Nedergaard, J. Norepinephrine induces vascular endothelial growth factor gene expression in brown adipocytes through a β-adrenoreceptor–cAMP–protein kinase A pathway involving Src but independently of Erk1/2. J. Biol. Chem. 275, 13802–13811 (2000).

    CAS  PubMed  Google Scholar 

  37. 37

    Lutgendorf, S. K. et al. Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines. Clin. Cancer Res. 9, 4514–4521 (2003).

    CAS  PubMed  Google Scholar 

  38. 38

    Masur, K., Niggemann, B., Zanker, K. S. & Entschladen, F. Norepinephrine-induced migration of SW 480 colon carcinoma cells is inhibited by β-blockers. Cancer Res. 61, 2866–2869 (2001).

    CAS  PubMed  Google Scholar 

  39. 39

    McDonald, P. H. & Lefkowitz, R. J. β-Arrestins: new roles in regulating heptahelical receptors' functions. Cell Signal. 13, 683–689 (2001).

    CAS  PubMed  Google Scholar 

  40. 40

    Abramovitch, R. et al. A pivotal role of cyclic AMP-responsive element binding protein in tumor progression. Cancer Res. 64, 1338–1346 (2004).

    CAS  PubMed  Google Scholar 

  41. 41

    Lang, K. et al. Induction of a metastatogenic tumor cell type by neurotransmitters and its pharmacological inhibition by established drugs. Int. J. Cancer 112, 231–238 (2004).

    CAS  PubMed  Google Scholar 

  42. 42

    Jean, D. & Bar-Eli, M. Regulation of tumor growth and metastasis of human melanoma by the CREB transcription factor family. Mol. Cell. Biochem. 212, 19–28 (2000).

    CAS  PubMed  Google Scholar 

  43. 43

    de Rooij, J. et al. Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396, 474–477 (1998).

    CAS  PubMed  Google Scholar 

  44. 44

    Enserink, J. M. et al. The cAMP–Epac–Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the α3β1 integrin but not the α6β4 integrin. J. Biol. Chem. 279, 44889–44896 (2004).

    CAS  PubMed  Google Scholar 

  45. 45

    Distelhorst, C. W. Recent insights into the mechanism of glucocorticosteroid-induced apoptosis. Cell Death Differ. 9, 6–19 (2002).

    CAS  PubMed  Google Scholar 

  46. 46

    Herr, I. et al. Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas. Cancer Res. 63, 3112–3120 (2003).

    CAS  PubMed  Google Scholar 

  47. 47

    Wu, W. et al. Microarray analysis reveals glucocorticoid-regulated survival genes that are associated with inhibition of apoptosis in breast epithelial cells. Cancer Res. 64, 1757–1764 (2004).

    CAS  PubMed  Google Scholar 

  48. 48

    Nakane, T. et al. Effects of IL-1 and cortisol on β-adrenergic receptors, cell proliferation, and differentiation in cultured human A549 lung tumor cells. J. Immunol. 145, 260–266 (1990).

    CAS  PubMed  Google Scholar 

  49. 49

    Dave, J. R. et al. Chronic sustained stress increases levels of anterior pituitary prolactin mRNA. Pharmacol. Biochem. Behav. 67, 423–431 (2000).

    CAS  PubMed  Google Scholar 

  50. 50

    Almeida, S. A., Petenusci, S. O., Franci, J. A., Rosa e Silva, A. A. & Carvalho, T. L. Chronic immobilization-induced stress increases plasma testosterone and delays testicular maturation in pubertal rats. Andrologia 32, 7–11 (2000).

    CAS  PubMed  Google Scholar 

  51. 51

    Young, W. S. 3rd & Lightman, S. L. Chronic stress elevates enkephalin expression in the rat paraventricular and supraoptic nuclei. Brain Res. Mol. Brain Res. 13, 111–117 (1992).

    CAS  PubMed  Google Scholar 

  52. 52

    Clevenger, C. V., Furth, P. A., Hankinson, S. E. & Schuler, L. A. The role of prolactin in mammary carcinoma. Endocr. Rev. 24, 1–27 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Pequeux, C. et al. Oxytocin- and vasopressin-induced growth of human small-cell lung cancer is mediated by the mitogen-activated protein kinase pathway. Endocr. Relat. Cancer 11, 871–885 (2004).

    CAS  PubMed  Google Scholar 

  54. 54

    Pequeux, C. et al. Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through autocrine/paracrine signaling. Cancer Res. 62, 4623–4629 (2002).

    CAS  PubMed  Google Scholar 

  55. 55

    Chakroborty, D. et al. Depleted dopamine in gastric cancer tissues: dopamine treatment retards growth of gastric cancer by inhibiting angiogenesis. Clin. Cancer Res. 10, 4349–4356 (2004).

    CAS  PubMed  Google Scholar 

  56. 56

    Basu, S. et al. The neurotransmitter dopamine inhibits angiogenesis induced by vascular permeability factor/vascular endothelial growth factor. Nature Med. 7, 569–574 (2001).

    CAS  PubMed  Google Scholar 

  57. 57

    Sephton, S. & Spiegel, D. Circadian disruption in cancer: a neuroendocrine-immune pathway from stress to disease? Brain Behav. Immun. 17, 321–328 (2003).

    CAS  PubMed  Google Scholar 

  58. 58

    Sephton, S. E., Sapolsky, R. M., Kraemer, H. C. & Spiegel, D. Diurnal cortisol rhythm as a predictor of breast cancer survival. J. Natl Cancer Inst. 92, 994–1000 (2000).

    CAS  PubMed  Google Scholar 

  59. 59

    Chrousos, G. P. & Gold, P. W. A healthy body in a healthy mind — and vice versa — the damaging power of “uncontrollable” stress. J. Clin. Endocrinol. Metab. 83, 1842–1845 (1998).

    CAS  PubMed  Google Scholar 

  60. 60

    Filipski, E. et al. Host circadian clock as a control point in tumor progression. J. Natl Cancer Inst. 94, 690–697 (2002).

    PubMed  Google Scholar 

  61. 61

    Schernhammer, E. S. et al. Night-shift work and risk of colorectal cancer in the nurses' health study. J. Natl Cancer Inst. 95, 825–828 (2003).

    PubMed  Google Scholar 

  62. 62

    Fu, L. & Lee, C. C. The circadian clock: pacemaker and tumour suppressor. Nature Rev. Cancer 3, 350–361 (2003).

    CAS  Google Scholar 

  63. 63

    Fu, L., Pelicano, H., Liu, J., Huang, P. & Lee, C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111, 41–50 (2002).

    CAS  PubMed  Google Scholar 

  64. 64

    Mormont, M. C. & Levi, F. Circadian-system alterations during cancer processes: a review. Int. J. Cancer 70, 241–247 (1997).

    CAS  PubMed  Google Scholar 

  65. 65

    Mormont, M. C. et al. Marked 24-h-rest–activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status. Clin. Cancer Res. 6, 3038–3045 (2000).

    CAS  PubMed  Google Scholar 

  66. 66

    Kronfol, Z., Nair, M., Zhang, Q., Hill, E. E. & Brown, M. B. Circadian immune measures in healthy volunteers: relationship to hypothalamic–pituitary–adrenal axis hormones and sympathetic neurotransmitters. Psychosom. Med. 59, 42–50 (1997).

    CAS  PubMed  Google Scholar 

  67. 67

    Rich, T. et al. Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest–activity patterns in patients with metastatic colorectal cancer. Clin. Cancer Res. 11, 1757–1764 (2005).

    CAS  PubMed  Google Scholar 

  68. 68

    Balkwill, F. & Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 357, 539–545 (2001).

    CAS  PubMed  Google Scholar 

  69. 69

    Blask, D. E., Sauer, L. A. & Dauchy, R. T. Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy. Curr. Top. Med. Chem. 2, 113–132 (2002).

    CAS  PubMed  Google Scholar 

  70. 70

    Sanchez-Barcelo, E. J., Cos, S., Fernandez, R. & Mediavilla, M. D. Melatonin and mammary cancer: a short review. Endocr. Relat. Cancer 10, 153–159 (2003).

    CAS  PubMed  Google Scholar 

  71. 71

    Jensen, M. M. The influence of stress on murine leukemia virus infection. Proc. Soc. Exp. Biol. Med. 127, 610–614 (1968).

    CAS  PubMed  Google Scholar 

  72. 72

    Justice, A. Review of the effects of stress on cancer in laboratory animals: importance of time of stress application and type of tumor. Psychol. Bull. 98, 108–138 (1985).

    CAS  PubMed  Google Scholar 

  73. 73

    Riley, V. Psychoneuroendocrine influences on immunocompetence and neoplasia. Science 212, 1100–1109 (1981).

    CAS  PubMed  Google Scholar 

  74. 74

    Rowse, G. L., Weinberg, J., Bellward, G. D. & Emerman, J. T. Endocrine mediation of psychosocial stressor effects on mouse mammary tumor growth. Cancer Lett. 65, 85–93 (1992).

    CAS  PubMed  Google Scholar 

  75. 75

    Romero, L. et al. A possible mechanism by which stress accelerates growth of virally-derived tumors. Proc. Natl Acad. Sci. USA 89, 11084–11087 (1992).

    CAS  PubMed  Google Scholar 

  76. 76

    McGrath, C. M., Prass, W. A., Maloney, T. M. & Jones, R. F. Induction of endogenous mammary tumor virus expression during hormonal induction of mammary adenoacanthomas and carcinomas of BALB/c female mice. J. Natl Cancer Inst. 67, 841–852 (1981).

    CAS  PubMed  Google Scholar 

  77. 77

    zur Hausen, H. Viruses in human cancers. Science 254, 1167–1173 (1991).

    CAS  PubMed  Google Scholar 

  78. 78

    Glaser, R. et al. Stress-related activation of Epstein–Barr virus. Brain Behav. Immun. 5, 219–232 (1991).

    CAS  PubMed  Google Scholar 

  79. 79

    Stowe, R. P., Pierson, D. L. & Barrett, D. T. Elevated stress hormone levels relate to Epstein–Barr Virus reactivation in astronauts. Psychosom. Med. 63, 891–895 (2001).

    CAS  PubMed  Google Scholar 

  80. 80

    Cacioppo, J. T. et al. Autonomic and glucocorticoid associations with the steady-state expression of latent Epstein–Barr Virus. Horm. Behav. 42, 32–41 (2002).

    CAS  PubMed  Google Scholar 

  81. 81

    Glaser, R., Kutz, L. A., MacCallum, R. C. & Malarkey, W. B. Hormonal modulation of Epstein–Barr virus replication. Neuroendocrinology 62, 356–361 (1995).

    CAS  PubMed  Google Scholar 

  82. 82

    Bromberg-White, J. L. & Meyers, C. Comparison of the basal and glucocorticoid-inducible activities of the upstream regulatory regions of HPV18 and HPV31 in multiple epithelial cell lines. Virology 306, 197–202 (2003).

    CAS  PubMed  Google Scholar 

  83. 83

    Mittal, R., Pater, A. & Pater, M. M. Multiple human papillomavirus type 16 glucocorticoid response elements functional for transformation, transient expression, and DNA–protein interactions. J. Virol. 67, 5656–5659 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84

    Gloss, B. et al. The upstream regulatory region of the human papilloma virus-16 contains an E2 protein-independent enhancer which is specific for cervical carcinoma cells and regulated by glucocorticoid hormones. EMBO J. 6, 3735–3743 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Pater, M. M., Hughes, G. A., Hyslop, D. E., Nakshatri, H. & Pater, A. Glucocorticoid-dependent oncogenic transformation by type 16 but not type 11 human papilloma virus DNA. Nature 335, 832–835 (1988).

    CAS  PubMed  Google Scholar 

  86. 86

    Bartholomew, J. S. et al. Integration of high-risk human papillomavirus DNA is linked to the down-regulation of class I human leukocyte antigens by steroid hormones in cervical tumor cells. Cancer Res. 57, 937–942 (1997).

    CAS  PubMed  Google Scholar 

  87. 87

    Coker, A. L., Bond, S., Madeleine, M. M., Luchok, K. & Pirisi, L. Psychosocial stress and cervical neoplasia risk. Psychosom. Med. 65, 644–651 (2003).

    PubMed  Google Scholar 

  88. 88

    Pereira, D. B. et al. Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus. Psychosom. Med. 65, 427–434 (2003).

    PubMed  Google Scholar 

  89. 89

    Pater, M. M. & Pater, A. RU486 inhibits glucocorticoid hormone-dependent oncogenesis by human papillomavirus type 16 DNA. Virology 183, 799–802 (1991).

    CAS  PubMed  Google Scholar 

  90. 90

    Chou, C. K., Wang, L. H., Lin, H. M. & Chi, C. W. Glucocorticoid stimulates hepatitis B viral gene expression in cultured human hepatoma cells. Hepatology 16, 13–18 (1992).

    CAS  PubMed  Google Scholar 

  91. 91

    Kamradt, M. C., Mohideen, N. & Vaughan, A. T. RU486 increases radiosensitivity and restores apoptosis through modulation of HPV E6/E7 in dexamethasone-treated cervical carcinoma cells. Gynecol. Oncol. 77, 177–182 (2000).

    CAS  PubMed  Google Scholar 

  92. 92

    Tur-Kaspa, R., Burk, R. D., Shaul, Y. & Shafritz, D. A. Hepatitis B virus DNA contains a glucocorticoid-responsive element. Proc. Natl Acad. Sci. USA 83, 1627–1631 (1986).

    CAS  PubMed  Google Scholar 

  93. 93

    Chayama, K. et al. A pilot study of corticosteroid priming for lymphoblastoid interferon α in patients with chronic hepatitis C. Hepatology 23, 953–957 (1996).

    CAS  PubMed  Google Scholar 

  94. 94

    Magy, N. et al. Effects of corticosteroids on HCV infection. Int. J. Immunopharmacol. 21, 253–261 (1999).

    CAS  PubMed  Google Scholar 

  95. 95

    Yokosuka, O. Role of steroid priming in the treatment of chronic hepatitis B. J. Gastroenterol. Hepatol. 15, E41–E45 (2000).

    CAS  PubMed  Google Scholar 

  96. 96

    Cole, S. W. et al. Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity. Proc. Natl Acad. Sci. USA 98, 12695–12700 (2001).

    CAS  PubMed  Google Scholar 

  97. 97

    Cole, S. W., Jamieson, B. D. & Zack, J. A. cAMP externalizes lymphocyte CXCR4: implications for chemotaxis and HIV infection. J. Immunol. 162, 1392–1400 (1999).

    CAS  PubMed  Google Scholar 

  98. 98

    Cole, S. W., Korin, Y. D., Fahey, J. L. & Zack, J. A. Norepinephrine accelerates HIV replication via protein kinase A-dependent effects on cytokine production. J. Immunol. 161, 610–616 (1998).

    CAS  PubMed  Google Scholar 

  99. 99

    Killebrew, D. & Shiramizu, B. Pathogenesis of HIV-associated non-Hodgkin lymphoma. Curr. HIV Res. 2, 215–221 (2004).

    CAS  PubMed  Google Scholar 

  100. 100

    Chang, M. et al. β Adrenoreceptors reactivate Kaposi's Sarcoma-associated Herpesvirus lytic replication via PKA-dependent control of viral RTA. J. Virol. 79, 13538–13547 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101

    Turgeman, H. & Aboud, M. Evidence that protein kinase A activity is required for the basal and tax-stimulated transcriptional activity of human T-cell leukemia virus type-I-long terminal repeat. FEBS Lett. 428, 183–187 (1998).

    CAS  PubMed  Google Scholar 

  102. 102

    Marsland, A. L., Cohen, S., Rabin, B. S. & Manuck, S. B. Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults. Health Psychol. 20, 4–11 (2001).

    CAS  PubMed  Google Scholar 

  103. 103

    Glaser, R. et al. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom. Med. 54, 22–29 (1992).

    CAS  PubMed  Google Scholar 

  104. 104

    Kinzler, K. W. & Vogelstein, B. The Genetic Basis of Human Cancer (McGraw–Hill, Toronto, 1998).

    Google Scholar 

  105. 105

    Dhabhar, F. S. & McEwen, B. S. Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking. Brain Behav. Immun. 11, 286–306 (1997).

    CAS  PubMed  Google Scholar 

  106. 106

    Elenkov, I. J. Systemic stress-induced Th2 shift and its clinical implications. Int. Rev. Neurobiol. 52, 163–186 (2002).

    CAS  PubMed  Google Scholar 

  107. 107

    Glaser, R. et al. Evidence for a shift in the Th-1 to Th-2 cytokine response associated with chronic stress and aging. J. Gerontol. A Biol. Sci. Med. Sci. 56, M477–M482 (2001).

    CAS  PubMed  Google Scholar 

  108. 108

    Felten, S. & Felten, D. in Psychoneuroimmunology (eds Ader, R., Felten, D. & Cohen, N.) 27–71 (St. Louis, Montana, 1991).

    Google Scholar 

  109. 109

    Dhabhar, F. S. & McEwen, B. S. Stress-induced enhancement of antigen-specific cell-mediated immunity. J. Immunol. 156, 2608–2615 (1996).

    CAS  PubMed  Google Scholar 

  110. 110

    Saul, A. N. et al. Chronic stress and susceptibility to skin cancer. J. Natl Cancer Inst. 97, 1760–1767 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111

    Kalinichenko, V. V., Mokyr, M. B., Graf, L. H. Jr, Cohen, R. L. & Chambers, D. A. Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a β-adrenergic receptor mechanism and decreased TNF-α gene expression. J. Immunol. 163, 2492–2499 (1999).

    CAS  PubMed  Google Scholar 

  112. 112

    Cook-Mills, J. M., Cohen, R. L., Perlman, R. L. & Chambers, D. A. Inhibition of lymphocyte activation by catecholamines: evidence for a non-classical mechanism of catecholamine action. Immunology 85, 544–549 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. 113

    Cook-Mills, J. M., Mokyr, M. B., Cohen, R. L., Perlman, R. L. & Chambers, D. A. Neurotransmitter suppression of the in vitro generation of a cytotoxic T lymphocyte response against the syngeneic MOPC-315 plasmacytoma. Cancer Immunol. Immunother. 40, 79–87 (1995).

    CAS  PubMed  Google Scholar 

  114. 114

    Shi, Y. et al. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology. Brain Behav. Immun. 17 (Suppl.), S18–S26 (2003).

    CAS  PubMed  Google Scholar 

  115. 115

    Pollock, R. E., Lotzova, E. & Stanford, S. D. Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity. Arch. Surg. 126, 338–342 (1991).

    CAS  PubMed  Google Scholar 

  116. 116

    Andersen, B. L. et al. Stress and immune responses after surgical treatment for regional breast cancer. J. Natl Cancer Inst. 90, 30–36 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. 117

    Lutgendorf, S. K. et al. Social support, distress, and natural killer cell activity in ovarian cancer patients. J. Clin. Oncol. 23, 7106–7113 (2005).

    Google Scholar 

  118. 118

    Levy, S. M. et al. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. Psychosom. Med. 52, 73–85 (1990).

    CAS  PubMed  Google Scholar 

  119. 119

    McGregor, B. A. et al. Cognitive-behavioral stress management increases benefit finding and immune function among women with early-stage breast cancer. J. Psychosom. Res. 56, 1–8 (2004).

    PubMed  Google Scholar 

  120. 120

    Sephton, S., Koopman, C., Schaal, M., Thoresen, C. & Spiegel, D. Spiritual expression and immune status in women with metastatic breast cancer: an exploratory study. Breast J. 7, 345–353 (2001).

    CAS  PubMed  Google Scholar 

  121. 121

    Christie, W. & Moore, C. The impact of humor on patients with cancer. Clin. J. Oncol. Nurs. 9, 211–218 (2005).

    PubMed  Google Scholar 

  122. 122

    Antoni, M. H. Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection: empirical support for a psychoneuroimmunological model. Stress 6, 173–188 (2003).

    CAS  PubMed  Google Scholar 

  123. 123

    Carlson, L. E., Speca, M., Patel, K. D. & Goodey, E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress and levels of cortisol, dehydroepiandrosterone sulfate (DHEAS) and melatonin in breast and prostate cancer outpatients. Psychoneuroendocrinology 29, 448–474 (2004).

    CAS  PubMed  Google Scholar 

  124. 124

    Andersen, B. L. et al. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. J. Clin. Oncol. 22, 3570–3580 (2004).

    PubMed  PubMed Central  Google Scholar 

  125. 125

    Lekander, M., Furst, C. J., Rotstein, S., Blomgren, H. & Fredrikson, M. Social support and immune status during and after chemotherapy for breast cancer. Acta Oncol. 35, 31–37 (1996).

    CAS  PubMed  Google Scholar 

  126. 126

    Fawzy, F. I., Canada, A. L. & Fawzy, N. W. Malignant melanoma: effects of a brief, structured psychiatric intervention on survival and recurrence at 10-year follow-up. Arch. Gen. Psychiatry 60, 100–103 (2003).

    PubMed  Google Scholar 

  127. 127

    Esterling, B. A. et al. Psychosocial modulation of antibody to Epstein–Barr viral capsid antigen and human herpesvirus type-6 in HIV-1-infected and at-risk gay men. Psychosom. Med. 54, 354–371 (1992).

    CAS  PubMed  Google Scholar 

  128. 128

    Antoni, M. H. et al. Randomized clinical trial of cognitive behavioral stress management on HIV viral load in gay men treated with HAART. Psychosom. Med. (in the press).

  129. 129

    Antoni, M. H. et al. Increases in a marker of immune system reconstitution are predated by decreases in 24-hour urinary cortisol output and depressed mood during a 10-week stress management intervention in symptomatic gay men. J. Psychosom. Res. 58, 3–13 (2005).

    PubMed  Google Scholar 

  130. 130

    Carlson, L. E., Speca, M., Patel, K. D. & Goodey, E. Mindfulness-based stress reduction in relation to quality of life, mood, symptoms of stress, and immune parameters in breast and prostate cancer outpatients. Psychosom. Med. 65, 571–581 (2003).

    PubMed  Google Scholar 

  131. 131

    Fawzy, F. I. et al. A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures. Arch. Gen. Psychiatry 47, 729–735 (1990).

    CAS  PubMed  Google Scholar 

  132. 132

    Spiegel, D., Bloom, J. R., Kraemer, H. C. & Gottheil, E. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2, 888–891 (1989).

    CAS  PubMed  Google Scholar 

  133. 133

    Goodwin, P. J. et al. The effect of group psychosocial support on survival in metastatic breast cancer. N. Engl. J. Med. 345, 1719–1726 (2001).

    CAS  PubMed  Google Scholar 

  134. 134

    Spiegel, D. Effects of psychotherapy on cancer survival. Nature Rev. Cancer 2, 383–389 (2002).

    CAS  Google Scholar 

  135. 135

    Perron, L., Bairati, I., Harel, F. & Meyer, F. Antihypertensive drug use and the risk of prostate cancer (Canada). Cancer Causes Control 15, 535–541 (2004).

    PubMed  Google Scholar 

  136. 136

    Algazi, M., Plu-Bureau, G., Flahault, A., Dondon, M. G. & Le, M. G. Could treatments with β-blockers be associated with a reduction in cancer risk? Rev. Epidemiol. Sante Publique 52, 53–65 (2004) (in French).

    CAS  PubMed  Google Scholar 

  137. 137

    Li, C. I. et al. Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65–79 years. Cancer 98, 1504–1513 (2003).

    PubMed  Google Scholar 

  138. 138

    Meier, C. R., Derby, L. E., Jick, S. S. & Jick, H. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Arch. Intern. Med. 160, 349–353 (2000).

    CAS  PubMed  Google Scholar 

  139. 139

    Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. 140

    Lieb, J. Antidepressants, eicosanoids and the prevention and treatment of cancer. A review. Prostaglandins Leukot. Essent. Fatty Acids 65, 233–239 (2001).

    CAS  PubMed  Google Scholar 

  141. 141

    Sapolsky, R. M. Why Zebras Don't Get Ulcers: A Guide to Stress, Stress-Related Diseases, and Coping (Freeman, New York, 1994).

    Google Scholar 

  142. 142

    Buchschacher, G. L. J. & Wong-Staal, F. in Cancer: Principles and Practice of Oncology (eds DeVita, V. T. J., Hellman, S. & Rosenberg, S. A.) 165–172 (Lippincott Williams & Wilkins, Philadelphia, 2005).

    Google Scholar 

  143. 143

    Howley, P. M., Ganem, D. & Kieff, E. in Cancer: Principles and Practice of Oncology (eds DeVita, V. T. J., Hellman, S. & Rosenberg, S. A.) 173–184 (Lippincott Williams & Wilkins, Philadelphia, 2005).

    Google Scholar 

  144. 144

    Steplewski, Z., Vogel, W. H., Ehya, H., Poropatich, C. & Smith, J. M. Effects of restraint stress on inoculated tumor growth and immune response in rats. Cancer Res. 45, 5128–5133 (1985).

    CAS  PubMed  Google Scholar 

  145. 145

    Teunis, M. A. et al. Reduced tumor growth, experimental metastasis formation, and angiogenesis in rats with a hyperreactive dopaminergic system. FASEB J. 16, 1465–1467 (2002).

    CAS  PubMed  Google Scholar 

  146. 146

    Palermo-Neto, J., de Oliveira Massoco, C. & Robespierre de Souza, W. Effects of physical and psychological stressors on behavior, macrophage activity, and Ehrlich tumor growth. Brain Behav. Immun. 17, 43–54 (2003).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge the support of several Institutes and Centers of the National Institutes of Health; National Cancer Institute (M.H.A., S.K.L., F.S.D., and A.K.S.), National Center for Complementary and Alternative Medicine (S.K.L.), National Institute of Allergy and Infectious Diseases (S.W.C. and F.S.D.) and National Institute of Mental Health (M.H.A.). The authors also acknowledge support received from the Dana Foundation (F.S.D.), Jonssen Comprehensive Cancer Center (S.W.C.) and Norman Cousins Center at the University of California, Los Angeles (S.W.C.). Preparation of this perspective was facilitated by support from the Division of Cancer Control and Populations Sciences at the National Cancer Institute. We are indebted to Wendy Nelson for her editorial review of the manuscript.

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National Cancer Institute

breast cancer

lung tumour

ovarian cancer

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Anil K. Sood's web page

NCI Cancer Control and Population Sciences web site

Steven Cole's web page

Susan Lutgendorf's web page

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Antoni, M., Lutgendorf, S., Cole, S. et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 6, 240–248 (2006). https://doi.org/10.1038/nrc1820

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