Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Cellular and Molecular Biology

Cancer-inducing niche: the force of chronic inflammation

British Journal of Cancer volume 127, pages 193–201 (2022)Cite this article

Subjects

Abstract

The growth of cancer tissue is thought to be considered driven by a small subpopulation of cells, so-called cancer stem cells (CSCs). CSCs are located at the apex of a hierarchy in a cancer tissue with self-renewal, differentiation and tumorigenic potential that produce the progeny in the tissue. Although CSCs are generally believed to play a critical role in the growth, metastasis, and recurrence of cancers, the origin of CSCs remains to be reconsidered. We hypothesise that, chronic diseases, including obesity and diabetes, establish the cancer-inducing niche (CIN) that drives the undifferentiated/progenitor cells into CSCs, which then develop malignant tumours in vivo. In this context, a CIN could be traced to chronic inflammation that involves long-lasting tissue damage and repair after being exposed to factors such as cytokines and growth factors. This must be distinguished from the cancer microenvironment, which is responsible for cancer maintenance. The concept of a CIN is most important for cancer prevention as well as cancer therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: An overview of the cancer initiation and development.
Fig. 2: Schematic drawing of the development of Cancer-inducing niche and stem cell alternation.
Fig. 3: Schematic drawing of inflammatory microenvironment in the liver depicting the immune responses of different cells.
Fig. 4: Scheme of cancer initiation from inflammation in pancreas.
Fig. 5: Ovarian cancer-inducing niches.

Similar content being viewed by others

Data availability

Not applicable.

References

  1. Boveri T. Zur Frage der Entstehung maligner Tumoren. Jena, Germany: Verlag von Gustav Fischer; 1914. p. 29–32.

  2. Bauer KH. Mutationstheorie der Geschwulst-Entstehung. Berlin: Julius Springer Verlag; 1928.

  3. Mackenzie I, Rous P. The experimental disclosure of latent neoplastic changes in tarred skin. J Exp Med. 1941;73:391–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Muller HJ. Detection of mutations in the second chromosome by use of the “sifter” stock. Dros Inf Serv. 1951;25:117–8.

    Google Scholar 

  5. Nordling CO. A new theory on the cancer-inducing mechanism. Br J Cancer. 1953;7:68–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Burdette WJ. The significance of mutation in relation to the origin of tumors: a review. Cancer Res. 1955;15:201–26.

    CAS  PubMed  Google Scholar 

  7. Fisher J. Multiple-mutation theory of carcinogenesis. Nature. 1958;181:651–52.

    Article  CAS  PubMed  Google Scholar 

  8. Burch PR. Mutation, autoimmunity, and ageing. Lancet 1963;2:299–300.

    Article  CAS  PubMed  Google Scholar 

  9. Burch PR. Genetic carrier frequency for lung cancer. Nature 1964;202:711–2.

    Article  CAS  PubMed  Google Scholar 

  10. Ashley DJB. The two “hit” and multiple “hit” theories of carcinogenesis. Br J Cancer. 1969;23:313–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Foulds L. Neoplastic development. New York: Academic; 1969 p. 72–74.

  12. Knudson AG. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68:820–3.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. Patterns of somatic mutation in human cancer genome. Nature. 2007;446:153–158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Roberts SA, Gordenin DA. Hypermutation in human cancer genomes: footprints and mechanisms. Nat Rev Cancer. 2014;14:786–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tomasetti C, Vogelstein B. Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015;347:78–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Soto AM, Sonnenschein C. The somatic mutation theory of cancer: growing problems with the paradigm? Bioessays 2004;26:1097–107.

    Article  CAS  PubMed  Google Scholar 

  17. Virchow R, Rudolf V. Die krankhaften Geschwülste: dreissig Vorlesungen, gehalten während des Wintersemesters 1862-1863 an der Universität zu Berlin. Vol 1–3. Berlin: Verlag von August Hirschwald; 1863.

  18. Balkwill F, Mantovani A. Inflammation, and cancer: back to Virchow? Lancet 2001;357:539–45.

    Article  CAS  PubMed  Google Scholar 

  19. Yamagiwa K, Ichikawa K. Experimental study of the pathogenesis of cancer. J Cancer Res. 1918;3:1–29.

    Google Scholar 

  20. Meizlish ML, Franklin RA, Zhou X, Medzhitov R. Tissue Homeostasis, and Inflammation. Annu Rev Immunol. 2021;39:557–81.

    Article  CAS  PubMed  Google Scholar 

  21. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.

    Article  CAS  PubMed  Google Scholar 

  22. Afify SM, Seno M. Conversion of stem cells to cancer stem cells: undercurrent of cancer initiation. Cancers (Basel). 2019;11(Mar):345.

    Article  CAS  Google Scholar 

  23. Bu P, Chen K-Y, Lipkin SM, Shen X. Asymmetric division: a marker for cancer stem cells? Oncotarget. 2013;4:950–1.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Yan T, Mizutani A, Chen L, Takaki M, Hiramoto Y, Matsuda S, et al. Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived extracellular vesicles. J Cancer. 2014;5(Jul):572–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Osman A, Oze M, Afify SM, Hassan G, El-Ghlban S, Nawara HM, et al. Tumor-associated macrophages derived from cancer stem cells. Acta Histochem. 2020;122:151628.

    Article  CAS  PubMed  Google Scholar 

  26. Osman A, Afify SM, Hassan G, Fu X, Seno A, Seno M. Revisiting cancer stem cells as the origin of cancer-associated cells in the tumor microenvironment: a hypothetical view from the potential of iPSCs. Cancers (Basel). 2020;12:879. 4

    Article  CAS  Google Scholar 

  27. Kumon K, Afify SM, Hassan G, Ueno S, Monzur S, Nawara HM, et al. Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2. Sci Rep. 2021;11:23977. 14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hassan G, Afify SM, Nair N, Kumon K, Osman A, Du J, et al. Hematopoietic cells derived from cancer stem cells generated from mouse induced pluripotent stem cells. Cancers (Basel). 2019;12:82. 29

    Article  CAS  Google Scholar 

  29. Chen L, Kasai T, Li Y, Sugii Y, Jin G, Okada M, et al. A model of cancer stem cells derived from mouse induced pluripotent stem cells. PLoS ONE. 2012;7:e33544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Calle AS, Nair N, Oo AK, Prieto-Vila M, Koga M, Khayrani AC, et al. A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm). Am J Cancer Res. 2016;6(Dec):2799–815.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Nair N, Calle AS, Zahra MH, Prieto-Vila M, Oo AKK, Hurley L, et al. A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment. Sci Rep. 2017;7(Jul):6838.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Afify SM, Sanchez Calle A, Hassan G, Kumon K, Nawara HM, Zahra MH, et al. A novel model of liver cancer stem cells developed from induced pluripotent stem cells. Br J Cancer. 2020;122(Apr):1378–90.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Du J, Xu Y, Sasada S, Oo AKK, Hassan G, Mahmud H, et al. Signaling inhibitors accelerate the conversion of mouse iPS cells into cancer stem cells in the tumor microenvironment. Sci Rep. 2020;10(Jun):9955.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hassan G, Ohara T, Afify SM, Kumon K, Zahra MH, Fu X, et al. Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways. J Exp Clin Cancer Res. 2022;41(Jan):29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer. 2013;13(Nov):759–71.

    Article  CAS  PubMed  Google Scholar 

  36. Hussain SP, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer. 2007;121(Dec):2373–80.

    Article  CAS  PubMed  Google Scholar 

  37. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428–35.

    Article  CAS  PubMed  Google Scholar 

  38. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017;9:7204–18.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hu W, Pasare C. Location, location, location: tissue-specific regulation of immune responses. J Leukoc Biol. 2013;94:409–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rivera A, Siracusa MC, Yap GS, Gause WC. Innate cell communication kick-starts pathogen-specific immunity. Nat Immunol. 2016;17(Apr):356–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Watanabe S, Alexander M, Misharin AV, Budinger GRS. The role of macrophages in the resolution of inflammation. J Clin Invest. 2019;129:2619–28.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Bulfone-Paus S, Nilsson G, Draber P, Blank U, Levi-Schaffer F. Positive and negative signals in mast cell activation. Trends Immunol. 2017;38(Sep):657–67.

    Article  CAS  PubMed  Google Scholar 

  43. Zhao H, Wu L, Yan G, Chen Y, Zhou M, Wu Y, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther. 2021;6(Jul):263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Palomino DC, Marti LC. Chemokines and immunity. Einstein (Sao Paulo). 2015;13:469–73.

    Article  Google Scholar 

  45. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol. 2015;7(Jan):a016303.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16(Sep-Oct):585–601.

    Article  PubMed  Google Scholar 

  47. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hu Y, Yan F, Ying L, Xu D. Emerging roles for epigenetic programming in the control of inflammatory signaling integration in heath and disease. Adv Exp Med Biol. 2017;1024:63–90.

    Article  CAS  PubMed  Google Scholar 

  49. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447:425–32.

    Article  CAS  PubMed  Google Scholar 

  50. Casaletto JB, McClatchey AI. Spatial regulation of receptor tyrosine kinases in development and cancer. Nat Rev Cancer. 2012;12(May):387–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Richmond A, Thomas HG. Purification of melanoma growth stimulatory activity. J Cell Physiol. 1986;129(Dec):375–84.

    Article  CAS  PubMed  Google Scholar 

  52. Fukuda A, Wang SC, Morris JP, Folias AE, Liou A, Kim GE, et al. Stat3 and MMP7 contribute to pancreatic ductal adenocarcinoma initiation and progression. Cancer Cell. 2011;19(Apr):441–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Grivennikov S, Karin E, Terzic J, Mucida D, Yu GY, Vallabhapurapu S, et al. IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. Cancer Cell. 2009;15(Feb):103–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lesina M, Kurkowski MU, Ludes K, Rose-John S, Treiber M, Klöppel G, et al. Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell. 2011;19(Apr):456–69.

    Article  CAS  PubMed  Google Scholar 

  55. Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, et al. gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell. 2009;15(Feb):91–102.

    Article  CAS  PubMed  Google Scholar 

  56. Waldner MJ, Foersch S, Neurath MF. Interleukin-6–a key regulator of colorectal cancer development. Int J Biol Sci. 2012;8:1248–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(Nov):798–809.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, et al. Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Invest. 2008;118(Feb):560–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Dang T, Liou GY. Macrophage cytokines enhance cell proliferation of normal prostate epithelial cells through activation of ERK and Akt. Sci Rep. 2018;8(May):7718.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(Jul):436–44.

    Article  CAS  PubMed  Google Scholar 

  61. Campregher C, Luciani MG, Gasche C. Activated neutrophils induce an hMSH2-dependent G2/M checkpoint arrest and replication errors at a (CA)13-repeat in colon epithelial cells. Gut. 2008;57(Jun):780–7.

    Article  CAS  PubMed  Google Scholar 

  62. Mills KD, Ferguson DO, Alt FW. The role of DNA breaks in genomic instability and tumorigenesis. Immunol Rev. 2003;194(Aug):77–95.

    Article  CAS  PubMed  Google Scholar 

  63. Takai A, Toyoshima T, Uemura M, Kitawaki Y, Marusawa H, Hiai H, et al. A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. Oncogene. 2009;28(Jan):469–78.

    Article  CAS  PubMed  Google Scholar 

  64. Okazaki IM, Kotani A, Honjo T. Role of AID in tumorigenesis. Adv Immunol. 2007;94:245–73.

    Article  CAS  PubMed  Google Scholar 

  65. Endo Y, Marusawa H, Kou T, Nakase H, Fujii S, Fujimori T, et al. Activation-induced cytidine deaminase links between inflammation and the development of colitis-associated colorectal cancers. Gastroenterology. 2008;135(Sep):889–98.

    Article  CAS  PubMed  Google Scholar 

  66. Yamanishi Y, Boyle DL, Rosengren S, Green DR, Zvaifler NJ, Firestein GS. Regional analysis of p53 mutations in rheumatoid arthritis synovium. Proc Natl Acad Sci USA. 2002;99(Jul):10025–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bishayee A. The role of inflammation and liver cancer. Adv Exp Med Biol. 2014;816:401–35.

    Article  CAS  PubMed  Google Scholar 

  68. Yang YM, Kim SY, Seki E. Inflammation and liver cancer: molecular mechanisms and therapeutic targets. Semin Liver Dis. 2019;39:26–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Sällberg M, Pasetto A. Liver, tumor and viral hepatitis: key players in the complex balance between tolerance and immune activation. Front Immunol. 2020;11(Mar):552.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Gehring AJ, Sun D, Kennedy PT, Nolte-‘t Hoen E, Lim SG, Wasser S, et al. The level of viral antigen presented by hepatocytes influences CD8 T-cell function. J Virol. 2007;81:2940–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dardalhon V, Korn T, Kuchroo VK, Anderson AC. Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun. 2008;31:252–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–32.

    Article  CAS  PubMed  Google Scholar 

  73. Zhang Y, Cobleigh MA, Lian JQ, Huang CX, Booth CJ, Bai XF, et al. A proinflammatory role for interleukin-22 in the immune response to hepatitis B virus. Gastroenterology. 2011;141:1897–906.

    Article  CAS  PubMed  Google Scholar 

  74. Kared H, Fabre T, Bedard N, Bruneau J, Shoukry NH. Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C. PLoS Pathog. 2013;9:e1003422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Zhao L, Tang Y, You Z, Wang Q, Liang S, Han X, et al. Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression. PLoS ONE. 2011;6:e18909.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485–517.

    Article  CAS  PubMed  Google Scholar 

  77. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441:235–38.

    Article  CAS  PubMed  Google Scholar 

  78. Del Prete G, De Carli M, Almerigogna F, Giudizi MG, Biagiotti R, Romagnani S. Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production. J Immunol. 1993;150:353–60.

    PubMed  Google Scholar 

  79. Mittrucker HW, Visekruna A, Huber M. Heterogeneity in the differentiation and function of CD8(+) T cells. Arch Immunol Ther Exp (Warsz). 2014;62:449–58.

    Article  CAS  Google Scholar 

  80. Hinrichs CS, Kaiser A, Paulos CM, Cassard L, Sanchez-Perez L, Heemskerk B, et al. Type 17 CD8+ T cells display enhanced antitumor immunity. Blood. 2009;114:596–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, et al. Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 2010;140(Jan):197–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jiang R, Tan Z, Deng L, Chen Y, Xia Y, Gao Y, et al. Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3. Hepatology. 2011;54(Sep):900–9.

    Article  CAS  PubMed  Google Scholar 

  83. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5(Oct):749–59.

    Article  CAS  PubMed  Google Scholar 

  85. Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-κB as the matchmaker. Nat Immunol. 2011;12(Jul):715–23.

    Article  CAS  PubMed  Google Scholar 

  86. Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431(Sep):461–6.

    Article  CAS  PubMed  Google Scholar 

  87. Pandol S, Edderkaoui M, Gukovsky I, Lugea A, Gukovskaya A. Desmoplasia of pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2009;7(Nov):S44–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Lunardi S, Jamieson NB, Lim SY, Griffiths KL, Carvalho-Gaspar M, Al-Assar O, et al. IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival. Oncotarget. 2014;5(Nov):11064–80.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Liou GY. Inflammatory cytokine signaling during development of pancreatic and prostate cancers. J Immunol Res. 2017;2017:7979637.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Storz P, Crawford HC. Carcinogenesis of pancreatic ductal adenocarcinoma. Gastroenterology. 2020;158(Jun):2072–81.

    Article  CAS  PubMed  Google Scholar 

  91. Steele CW, Jamieson NB, Evans TR, McKay CJ, Sansom OJ, Morton JP, et al. Exploiting inflammation for therapeutic gain in pancreatic cancer. Br J Cancer. 2013;108(Mar):997–1003.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Chang JH, Jiang Y, Pillarisetty VG. Role of immune cells in pancreatic cancer from bench to clinical application: an updated review. Med (Baltim). 2016;95(Dec):e5541.

    Article  CAS  Google Scholar 

  93. Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, et al. Interleukin-6 is required for pancreatic cancer progression by promoting MAPK signaling activation and oxidative stress resistance. Cancer Res. 2013;73(Oct):6359–74.

    Article  CAS  PubMed  Google Scholar 

  94. Inman KS, Francis AA, Murray NR. Complex role for the immune system in initiation and progression of pancreatic cancer. World J Gastroenterol. 2014;20(Aug):11160–81.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Swidnicka-Siergiejko AK, Gomez-Chou SB, Cruz-Monserrate Z, Deng D, Liu Y, Huang H, et al. Chronic inflammation initiates multiple forms of K-Ras-independent mouse pancreatic cancer in the absence of TP53. Oncogene. 2017;36(Jun):3149–58.

    Article  CAS  PubMed  Google Scholar 

  96. Kong B, Bruns P, Behler NA, Chang L, Schlitter AM, Cao J, et al. Dynamic landscape of pancreatic carcinogenesis reveals early molecular networks of malignancy. Gut. 2018;67(Jan):146–56.

    Article  CAS  PubMed  Google Scholar 

  97. Lee KE, Bar-Sagi D. Oncogenic KRas suppresses inflammation-associated senescence of pancreatic ductal cells. Cancer Cell. 2010;18(Nov):448–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Li Y, He Y, Peng J, Su Z, Li Z, Zhang B, et al. Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer. Nat Cancer. 2021;2:49–65.

    Article  CAS  PubMed  Google Scholar 

  99. Lheureux S, Braunstein M, Oza AM. Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin. 2019;69(Jul):280–304.

    PubMed  Google Scholar 

  100. Prat J. New insights into ovarian cancer pathology. Ann Oncol. 2012;23(Sep):x111–7.

    Article  PubMed  Google Scholar 

  101. Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 S6(Oct):24–32.

    Article  Google Scholar 

  102. Shah NM, Lai PF, Imami N, Johnson MR. Progesterone-related immune modulation of pregnancy and labor. Front Endocrinol (Lausanne). 2019;10(Mar):198.

    Article  Google Scholar 

  103. Straub RH. The complex role of estrogens in inflammation. Endocr Rev. 2007;28(Aug):521–74.

    Article  CAS  PubMed  Google Scholar 

  104. Finn OJ. Cancer immunology. N. Engl J Med. 2008;358(Jun):2704–15.

    Article  CAS  PubMed  Google Scholar 

  105. Lin HW, Tu YY, Lin SY, Su WJ, Lin WL, Lin WZ, et al. Risk of ovarian cancer in women with pelvic inflammatory disease: a population-based study. Lancet Oncol. 2011;12(Sep):900–4.

    Article  PubMed  Google Scholar 

  106. Rasmussen CB, Jensen A, Albieri V, Andersen KK, Kjaer SK. Is Pelvic inflammatory disease a risk factor for ovarian cancer? Cancer Epidemiol Biomark Prev. 2017;26(Jan):104–9.

    Article  Google Scholar 

  107. Zhou Z, Zeng F, Yuan J, Tang J, Colditz GA, Tworoger SS, et al. Pelvic inflammatory disease and the risk of ovarian cancer: a meta-analysis. Cancer Causes Control. 2017;28(May):415–28.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Ingerslev K, Hogdall E, Schnack TH, Skovrider-Ruminski W, Hogdall C, Blaakaer J. The potential role of infectious agents and pelvic inflammatory disease in ovarian carcinogenesis. Infect Agent Cancer. 2017;12(May):25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Rasmussen CB, Jensen A, Albieri V, Andersen KK, Kjaer SK. Increased risk of borderline ovarian tumors in women with a history of pelvic inflammatory disease: a nationwide population-based cohort study. Gynecol Oncol. 2016;143(Nov):346–51.

    Article  PubMed  Google Scholar 

  110. Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N. Engl J Med. 2015;372(May):2039–48.

    Article  PubMed  Google Scholar 

  111. Curry A, Williams T, Penny ML. Pelvic inflammatory disease: diagnosis, management, and prevention. Am Fam Physician. 2019;100(Sep):357–64.

    PubMed  Google Scholar 

  112. Gradison M. Pelvic inflammatory disease. Am Fam Physician. 2012;85(Apr):791–6.

    PubMed  Google Scholar 

  113. Rasmussen SJ, Eckmann L, Quayle AJ, Shen L, Zhang YX, Anderson DJ, et al. Secretion of proinflammatory cytokines by epithelial cells in response to Chlamydia infection suggests a central role for epithelial cells in chlamydial pathogenesis. J Clin Invest. 1997;99(Jan):77–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Makepeace BL, Watt PJ, Heckels JE, Christodoulides M. Interactions of Neisseria gonorrhoeae with mature human macrophage opacity proteins influence production of proinflammatory cytokines. Infect Immun. 2001;69(Mar):1909–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Ramsey KH, Schneider H, Cross AS, Boslego JW, Hoover DL, Staley TL, et al. Inflammatory cytokines produced in response to experimental human gonorrhea. J Infect Dis. 1995;172(Jul):186–91.

    Article  CAS  PubMed  Google Scholar 

  116. Cousins FL, Dorien OF, Gargett CE. Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis. Best Pr Res Clin Obstet Gynaecol. 2018;50(Jul):27–38.

    Article  Google Scholar 

  117. Anglesio MS, Yong PJ. Endometriosis-associated ovarian cancers. Clin Obstet Gynecol. 2017;60(Dec):711–27.

    Article  PubMed  Google Scholar 

  118. Worley MJ, Welch WR, Berkowitz RS, Ng SW. Endometriosis-associated ovarian cancer: a review of pathogenesis. Int J Mol Sci. 2013;14(Mar):5367–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N. Engl J Med. 2020;382(Mar):1244–56.

    Article  CAS  PubMed  Google Scholar 

  120. Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(Aug):441–7.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Melin A, Sparén P, Persson I, Bergqvist A. Endometriosis and the risk of cancer with special emphasis on ovarian cancer. Hum Reprod. 2006;21(May):1237–42.

    Article  CAS  PubMed  Google Scholar 

  122. Wei JJ, William J, Bulun S. Endometriosis and ovarian cancer: a review of clinical, pathologic, and molecular aspects. Int J Gynecol Pathol. 2011;30(Nov):553–68.

    Article  PubMed  PubMed Central  Google Scholar 

  123. Yamaguchi K, Mandai M, Toyokuni S, Hamanishi J, Higuchi T, Takakura K, et al. Contents of endometriotic cysts, especially the high concentration of free iron, are a possible cause of carcinogenesis in the cysts through the iron-induced persistent oxidative stress. Clin Cancer Res. 2008;14(Jan):32–40.

    Article  CAS  PubMed  Google Scholar 

  124. Zanetta GM, Webb MJ, Li H, Keeney GL. Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis. Gynecol Oncol. 2000;79:18–22.

    Article  CAS  PubMed  Google Scholar 

  125. Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;25:461. 5

    Google Scholar 

  126. Chou CH, Wei LH, Kuo ML, Huang YJ, Lai KP, Chen CA, et al. Up-regulation of interleukin-6 in human ovarian cancer cell via a Gi/PI3K-Akt/NF-kappaB pathway by lysophosphatidic acid, an ovarian cancer-activating factor. Carcinogenesis. 2005;26:45–52.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan

    Said M. Afify, Ghmkin Hassan, Akimasa Seno & Masaharu Seno

  2. Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufia University, Shebin El Koum-Menoufia, 32511, Egypt

    Said M. Afify

  3. Okayama University Research Laboratory of Stem Cell Engineering in Detroit, IBio, Wayne State University, Detroit, MI, USA

    Akimasa Seno & Masaharu Seno

Authors
  1. Said M. Afify
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ghmkin Hassan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akimasa Seno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masaharu Seno
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MS and SMA developed the concept and performed the literature. SMA wrote the manuscript. GH and AS assisted in collecting the draft. MS and SMA revised the final manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Said M. Afify or Masaharu Seno.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afify, S.M., Hassan, G., Seno, A. et al. Cancer-inducing niche: the force of chronic inflammation. Br J Cancer 127, 193–201 (2022). https://doi.org/10.1038/s41416-022-01775-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-022-01775-w

This article is cited by

Search

Advanced search

Quick links