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.

  • Article
  • Published:

Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer

Cancer Gene Therapy volume 29, pages 597–611 (2022)Cite this article

Subjects

Abstract

Medical marijuana has been approved by the FDA for treating chemotherapy-induced nausea and vomiting. However, less is known about its direct effects on tumor cells and the tumor microenvironment. In this study, RNA-sequencing datasets in the NCBI GEO repository were first analyzed; upregulation of cannabinoid receptors was observed in both primary and metastatic colorectal cancer (CRC) tumor tissues. An increase of cannabinoid receptors was also found in patients with CRC, azoxymethane/dextran sulfate sodium-induced CRC and CRC metastatic mouse models. Δ9-Tetrahydrocannabinol (Δ9-THC)-induced tumor progression in both primary and metastatic mouse models and also increased angiogenesis. A human growth factor antibody array indicated that Δ9-THC promoted the secretion of angiogenic growth factors in CRC, leading to the induction of tube formation and migration in human-induced pluripotent stem cell-derived vascular endothelial cells. The nuclear translocation of STAT1 played important roles in Δ9-THC-induced angiogenesis and tumor progression. Pharmacological treatment with STAT1 antagonist or abrogation of STAT1 with CRISPR/Cas9-based strategy rescued those effects of Δ9-THC in CRC. This study demonstrates that marijuana might increase the risk of CRC progression and that inhibition of STAT1 is a potential strategy for attenuating these side effects.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Expressions of CNR1 and CNR2 in colorectal cancer.
Fig. 2: Effect of Δ9-THC on colorectal tumor growth in xenograft mouse models.
Fig. 3: Effect of Δ9-THC on colorectal tumor metastasis in a tail vein-injected mouse model.
Fig. 4: Effect of Δ9-THC on angiogenesis in colorectal cancer in vitro and in vivo.
Fig. 5: Roles of STAT1 in Δ9-THC-induced angiogenesis in colorectal cancer.
Fig. 6: Knockout of STAT1 by CRISPR/Cas9 system disrupts the interaction between colorectal cancer cells and vascular endothelial cells.
Fig. 7: Interaction between cancer cells and vascular endothelial cells through STAT1-dependent angiogenesis and tumor growth in colorectal cancer.

Similar content being viewed by others

References

  1. Thomas G, Kloner RA, Rezkalla S. Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know. Am J Cardiol. 2014;113:187–90.

    Article  CAS  PubMed  Google Scholar 

  2. Sznitman SR, Bretteville-Jensen AL. Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies. Harm Reduct J. 2015;12:46.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313:2456–73.

    Article  CAS  PubMed  Google Scholar 

  4. Pacula RL, Smart R. Medical marijuana and marijuana legalization. Annu Rev Clin Psychol. 2017;13:397–419.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Badowski ME, Yanful PK. Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer. Ther Clin Risk Manag. 2018;14:643–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pergam SA, Woodfield MC, Lee CM, Cheng GS, Baker KK, Marquis SR, et al. Cannabis use among patients at a comprehensive cancer center in a state with legalized medicinal and recreational use. Cancer. 2017;123:4488–97.

    Article  CAS  PubMed  Google Scholar 

  7. Calcaterra SL, Burnett-Hartman AN, Powers JD, Corley DA, McMullen CM, Pawloski PA, et al. A population-based survey to assess the association between cannabis and quality of life among colorectal cancer survivors. BMC Cancer. 2020;20:373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Martell K, Fairchild A, LeGerrier B, Sinha R, Baker S, Liu H, et al. Rates of cannabis use in patients with cancer. Curr Oncol. 2018;25:219–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther Adv Psychopharmacol. 2012;2:241–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hoffman AF, Lupica CR. Synaptic targets of Delta9-tetrahydrocannabinol in the central nervous system. Cold Spring Harb Perspect Med. 2013;3:a012237.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Turu G, Hunyady L. Signal transduction of the CB1 cannabinoid receptor. J Mol Endocrinol. 2010;44:75–85.

    Article  CAS  PubMed  Google Scholar 

  12. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 1990;346:561–4.

    Article  CAS  PubMed  Google Scholar 

  13. Liu QR, Pan CH, Hishimoto A, Li CY, Xi ZX, Llorente-Berzal A, et al. Species differences in cannabinoid receptor 2 (CNR2 gene): identification of novel human and rodent CB2 isoforms, differential tissue expression and regulation by cannabinoid receptor ligands. Genes Brain Behav. 2009;8:519–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Haspula D, Clark MA. Cannabinoid receptors: an update on cell signaling, pathophysiological roles and therapeutic opportunities in neurological, cardiovascular, and inflammatory diseases. Int J Mol Sci. 2020;21:7693.

    Article  PubMed Central  CAS  Google Scholar 

  15. Bifulco M, Di Marzo V. Targeting the endocannabinoid system in cancer therapy: a call for further research. Nat Med. 2002;8:547–50.

    Article  CAS  PubMed  Google Scholar 

  16. Moreno E, Cavic M, Krivokuca A, Casado V, Canela E. The endocannabinoid system as a target in cancer diseases: are we there yet? Front Pharm. 2019;10:339.

    Article  CAS  Google Scholar 

  17. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.

    Article  CAS  PubMed  Google Scholar 

  18. Jang S, Collin de l’Hortet A, Soto-Gutierrez A. Induced pluripotent stem cell-derived endothelial cells: overview, current advances, applications, and future directions. Am J Pathol. 2019;189:502–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Edwards MS, Chadda SD, Zhao Z, Barber BL, Sykes DP. A systematic review of treatment guidelines for metastatic colorectal cancer. Colorectal Dis. 2012;14:e31–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14:1014–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer. 2017;17:457–74.

    Article  PubMed  CAS  Google Scholar 

  22. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer. 2003;3:401–10.

    Article  CAS  PubMed  Google Scholar 

  23. Vestweber D. VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Arterioscler Thromb Vasc Biol. 2008;28:223–32.

    Article  CAS  PubMed  Google Scholar 

  24. Lamalice L, Le Boeuf F, Huot J. Endothelial cell migration during angiogenesis. Circ Res. 2007;100:782–94.

    Article  CAS  PubMed  Google Scholar 

  25. Ghasemiesfe M, Barrow B, Leonard S, Keyhani S, Korenstein D. Association between marijuana use and risk of cancer: a systematic review and meta-analysis. JAMA Netw Open. 2019;2:e1916318.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hijiya N, Shibata T, Daa T, Hamanaka R, Uchida T, Matsuura K, et al. Overexpression of cannabinoid receptor 1 in esophageal squamous cell carcinoma is correlated with metastasis to lymph nodes and distant organs, and poor prognosis. Pathol Int. 2017;67:83–90.

    Article  CAS  PubMed  Google Scholar 

  27. Chung SC, Hammarsten P, Josefsson A, Stattin P, Granfors T, Egevad L, et al. A high cannabinoid CB(1) receptor immunoreactivity is associated with disease severity and outcome in prostate cancer. Eur J Cancer. 2009;45:174–82.

    Article  CAS  PubMed  Google Scholar 

  28. Michalski CW, Oti FE, Erkan M, Sauliunaite D, Bergmann F, Pacher P, et al. Cannabinoids in pancreatic cancer: correlation with survival and pain. Int J Cancer. 2008;122:742–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Messalli EM, Grauso F, Luise R, Angelini A, Rossiello R. Cannabinoid receptor type 1 immunoreactivity and disease severity in human epithelial ovarian tumors. Am J Obstet Gynecol. 2014;211:234 e1–6.

    Article  CAS  Google Scholar 

  30. Mukhopadhyay B, Schuebel K, Mukhopadhyay P, Cinar R, Godlewski G, Xiong K, et al. Cannabinoid receptor 1 promotes hepatocellular carcinoma initiation and progression through multiple mechanisms. Hepatology. 2015;61:1615–26.

    Article  CAS  PubMed  Google Scholar 

  31. Perez-Gomez E, Andradas C, Blasco-Benito S, Caffarel MM, Garcia-Taboada E, Villa-Morales M, et al. Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer. J Natl Cancer Inst. 2015;107:djv077.

    Article  PubMed  CAS  Google Scholar 

  32. Wang J, Xu Y, Zhu L, Zou Y, Kong W, Dong B, et al. Cannabinoid receptor 2 as a novel target for promotion of renal cell carcinoma prognosis and progression. J Cancer Res Clin Oncol. 2018;144:39–52.

    Article  CAS  PubMed  Google Scholar 

  33. Klein Nulent TJ, Van Diest PJ, van der Groep P, Leusink FK, Kruitwagen CL, Koole R, et al. Cannabinoid receptor-2 immunoreactivity is associated with survival in squamous cell carcinoma of the head and neck. Br J Oral Maxillofac Surg. 2013;51:604–9.

    Article  PubMed  Google Scholar 

  34. Xu S, Ma H, Bo Y, Shao M. The oncogenic role of CB2 in the progression of non-small-cell lung cancer. Biomed Pharmacother. 2019;117:109080.

    Article  CAS  PubMed  Google Scholar 

  35. Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: cancer anorexia-cachexia syndrome—when all you can eat is yourself. Nat Clin Pract Oncol. 2005;2:158–65.

    Article  CAS  PubMed  Google Scholar 

  36. Donohoe CL, Ryan AM, Reynolds JV. Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract. 2011;2011:601434.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bennani-Baiti N, Walsh D. Animal models of the cancer anorexia-cachexia syndrome. Support Care Cancer. 2011;19:1451–63.

    Article  PubMed  Google Scholar 

  38. Suzuki T, Von Haehling S, Springer J. Promising models for cancer-induced cachexia drug discovery. Expert Opin Drug Discov. 2020;15:627–37.

    Article  CAS  PubMed  Google Scholar 

  39. Baracos VE. Bridging the gap: are animal models consistent with clinical cancer cachexia? Nat Rev Clin Oncol. 2018;15:197–8.

    Article  PubMed  Google Scholar 

  40. Baltgalvis KA, Berger FG, Pena MM, Davis JM, Muga SJ, Carson JA. Interleukin-6 and cachexia in ApcMin/+ mice. Am J Physiol Regul Integr Comp Physiol. 2008;294:R393–401.

    Article  CAS  PubMed  Google Scholar 

  41. Moser AR, Luongo C, Gould KA, McNeley MK, Shoemaker AR, Dove WF. ApcMin: a mouse model for intestinal and mammary tumorigenesis. Eur J Cancer. 1995;31A:1061–4.

    Article  CAS  PubMed  Google Scholar 

  42. Tseng W, Leong X, Engleman E. Orthotopic mouse model of colorectal cancer. J Vis Exp. 2007;10:484.

    Google Scholar 

  43. Kondo H, Matsumoto J, Adachi K. Primary adenosquamous carcinoma of the cecum. Dig Liver Dis. 2012;44:268.

    Article  PubMed  Google Scholar 

  44. Loree JM, Pereira AAL, Lam M, Willauer AN, Raghav K, Dasari A, et al. Classifying colorectal cancer by tumor location rather than sidedness highlights a continuum in mutation profiles and consensus molecular subtypes. Clin Cancer Res. 2018;24:1062–72.

    Article  CAS  PubMed  Google Scholar 

  45. Siolas D, Hannon GJ. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 2013;73:5315–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Aparicio S, Hidalgo M, Kung AL. Examining the utility of patient-derived xenograft mouse models. Nat Rev Cancer. 2015;15:311–6.

    Article  CAS  PubMed  Google Scholar 

  47. Ballaro R, Costelli P, Penna F. Animal models for cancer cachexia. Curr Opin Support Palliat Care. 2016;10:281–7.

    Article  PubMed  Google Scholar 

  48. Tanaka Y, Eda H, Tanaka T, Udagawa T, Ishikawa T, Horii I, et al. Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. Cancer Res. 1990;50:2290–5.

    CAS  PubMed  Google Scholar 

  49. Aulino P, Berardi E, Cardillo VM, Rizzuto E, Perniconi B, Ramina C, et al. Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse. BMC Cancer. 2010;10:363.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Huot JR, Novinger LJ, Pin F, Bonetto A. HCT116 colorectal liver metastases exacerbate muscle wasting in a mouse model for the study of colorectal cancer cachexia. Dis Model Mech. 2020;13:dmm043166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Huot JR, Pin F, Essex AL, Bonetto A. MC38 tumors induce musculoskeletal defects in colorectal cancer. Int J Mol Sci. 2021;22:1486.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Bonetto A, Kays JK, Parker VA, Matthews RR, Barreto R, Puppa MJ, et al. Differential bone loss in mouse models of colon cancer cachexia. Front Physiol. 2016;7:679.

    PubMed  Google Scholar 

  53. Pisanti S, Picardi P, D’Alessandro A, Laezza C, Bifulco M. The endocannabinoid signaling system in cancer. Trends Pharm Sci. 2013;34:273–82.

    Article  CAS  PubMed  Google Scholar 

  54. Wilkie G, Sakr B, Rizack T. Medical marijuana use in oncology: a review. JAMA Oncol. 2016;2:670–5.

    Article  PubMed  Google Scholar 

  55. Hinz B, Ramer R. Anti-tumour actions of cannabinoids. Br J Pharm. 2019;176:1384–94.

    Article  CAS  Google Scholar 

  56. Kovalchuk O, Kovalchuk I. Cannabinoids as anticancer therapeutic agents. Cell Cycle. 2020;19:961–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Preet A, Ganju RK, Groopman JE. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene. 2008;27:339–46.

    Article  CAS  PubMed  Google Scholar 

  58. Greenhough A, Patsos HA, Williams AC, Paraskeva C. The cannabinoid delta(9)-tetrahydrocannabinol inhibits RAS-MAPK and PI3K-AKT survival signalling and induces BAD-mediated apoptosis in colorectal cancer cells. Int J Cancer. 2007;121:2172–80.

    Article  CAS  PubMed  Google Scholar 

  59. Schwope DM, Karschner EL, Gorelick DA, Huestis MA. Identification of recent cannabis use: whole-blood and plasma free and glucuronidated cannabinoid pharmacokinetics following controlled smoked cannabis administration. Clin Chem. 2011;57:1406–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Justinova Z, Goldberg SR, Heishman SJ, Tanda G. Self-administration of cannabinoids by experimental animals and human marijuana smokers. Pharm Biochem Behav. 2005;81:285–99.

    Article  CAS  Google Scholar 

  61. Chan GC, Hinds TR, Impey S, Storm DR. Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. J Neurosci. 1998;18:5322–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Armstrong JL, Hill DS, McKee CS, Hernandez-Tiedra S, Lorente M, Lopez-Valero I, et al. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Investig Dermatol. 2015;135:1629–37.

    Article  CAS  PubMed  Google Scholar 

  63. Ahmadi K, Roshan-Milani S, Asgharzadeh F, Pourjabali M, Fard AA. In vitro and in vivo pretreatment with selenium mitigates tetrahydrocannabinol-induced testicular cell apoptosis: the role of AKT and p53 pathways. Biol Trace Elem Res. 2021;199:2278–87.

    Article  CAS  PubMed  Google Scholar 

  64. Miyato H, Kitayama J, Yamashita H, Souma D, Asakage M, Yamada J, et al. Pharmacological synergism between cannabinoids and paclitaxel in gastric cancer cell lines. J Surg Res. 2009;155:40–7.

    Article  CAS  PubMed  Google Scholar 

  65. Martinez-Martinez E, Martin-Ruiz A, Martin P, Calvo V, Provencio M, Garcia JM. CB2 cannabinoid receptor activation promotes colon cancer progression via AKT/GSK3beta signaling pathway. Oncotarget. 2016;7:68781–91.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Liu C, Sadat SH, Ebisumoto K, Sakai A, Panuganti BA, Ren S. et al. Cannabinoids promote progression of HPV positive head and neck squamous cell carcinoma via p38 MAPK activation. Clin Cancer Res. 2020;26:2693–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Hart S, Fischer OM, Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res. 2004;64:1943–50.

    Article  CAS  PubMed  Google Scholar 

  68. McKallip RJ, Nagarkatti M, Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol. 2005;174:3281–9.

    Article  CAS  PubMed  Google Scholar 

  69. Khodarev NN, Roizman B, Weichselbaum RR. Molecular pathways: interferon/stat1 pathway: role in the tumor resistance to genotoxic stress and aggressive growth. Clin Cancer Res. 2012;18:3015–21.

    Article  CAS  PubMed  Google Scholar 

  70. Avalle L, Pensa S, Regis G, Novelli F, Poli V. STAT1 and STAT3 in tumorigenesis: a matter of balance. JAKSTAT. 2012;1:65–72.

    PubMed  PubMed Central  Google Scholar 

  71. Simpson JA, Al-Attar A, Watson NF, Scholefield JH, Ilyas M, Durrant LG. Intratumoral T cell infiltration, MHC class I and STAT1 as biomarkers of good prognosis in colorectal cancer. Gut. 2010;59:926–33.

    Article  CAS  PubMed  Google Scholar 

  72. Meissl K, Macho-Maschler S, Muller M, Strobl B. The good and the bad faces of STAT1 in solid tumours. Cytokine. 2017;89:12–20.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hix LM, Karavitis J, Khan MW, Shi YH, Khazaie K, Zhang M. Tumor STAT1 transcription factor activity enhances breast tumor growth and immune suppression mediated by myeloid-derived suppressor cells. J Biol Chem. 2013;288:11676–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Greenwood C, Metodieva G, Al-Janabi K, Lausen B, Alldridge L, Leng L, et al. Stat1 and CD74 overexpression is co-dependent and linked to increased invasion and lymph node metastasis in triple-negative breast cancer. J Proteom. 2012;75:3031–40.

    Article  CAS  Google Scholar 

  76. Zimmerman MA, Rahman NT, Yang D, Lahat G, Lazar AJ, Pollock RE, et al. Unphosphorylated STAT1 promotes sarcoma development through repressing expression of Fas and bad and conferring apoptotic resistance. Cancer Res. 2012;72:4724–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wei TT, Lin YT, Chen WS, Luo P, Lin YC, Shun CT, et al. Dual targeting of 3-hydroxy-3-methylglutaryl coenzyme A reductase and histone deacetylase as a therapy for colorectal cancer. EBioMedicine. 2016;10:124–36.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Wei TT, Lin YT, Tseng RY, Shun CT, Lin YC, Wu MS, et al. Prevention of colitis and colitis-associated colorectal cancer by a novel polypharmacological histone deacetylase inhibitor. Clin Cancer Res. 2016;22:4158–69.

    Article  CAS  PubMed  Google Scholar 

  79. Sayed N, Liu C, Ameen M, Himmati F, Zhang JZ, Khanamiri S. et al. Clinical trial in a dish using iPSCs shows lovastatin improves endothelial dysfunction and cellular cross-talk in LMNA cardiomyopathy. Sci Transl Med. 2020;12:eaax9276.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Huang DW, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 2007;35:W169–75.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Taiwan Human Disease Induced Pluripotent Stem Cell Service Consortium (Taiwan-iPSC consortium) for helping with iPSC generation. We are grateful for Dr. Ching-Chow Chen (National Taiwan University) for providing human CRC cells for this project. The authors would like to express their gratitude to the National Taiwan University College of Medicine for facility support.

Funding

This work was financially supported by the Ministry of Science and Technology (MOST) in Taiwan, under Grant MOST108-2636-B-002-007, MOST109-2636-B-002-007, and MOST110-2636-B-002-016. The authors would like to express their gratitude to the National Taiwan University College of Medicine for facility support.

Author information

Author notes

  1. These authors contributed equally: Cong-Kai Luo, Pei-Hsuan Chou.

Authors and Affiliations

  1. Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Cong-Kai Luo, Pei-Hsuan Chou, Shang-Kok Ng & Tzu-Tang Wei

  2. School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan

    Wen-Yen Lin

Authors
  1. Cong-Kai Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pei-Hsuan Chou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shang-Kok Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wen-Yen Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tzu-Tang Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

C.-K.L., P.-H.C., S.-K.N. and W.-Y.L.: collection and/or assembly of data, data analysis and interpretation; C.-K.L. and T.-T.W.: manuscript writing; T.-T.W.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.

Corresponding author

Correspondence to Tzu-Tang Wei.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luo, CK., Chou, PH., Ng, SK. et al. Cannabinoids orchestrate cross-talk between cancer cells and endothelial cells in colorectal cancer. Cancer Gene Ther 29, 597–611 (2022). https://doi.org/10.1038/s41417-021-00346-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-021-00346-0

This article is cited by

Search

Advanced search

Quick links