ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth

Authors

  • P H Nguyen Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • J Giraud Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • C Staedel Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • L Chambonnier Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • P Dubus Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • E Chevret Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • H Boeuf Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • X Gauthereau Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • B Rousseau Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • M Fevre Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • I Soubeyran Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • G Belleannée Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • S Evrad Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • D Collet Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • F Mégraud Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam
  • C Varon Faculty of Biotechnology Thai Nguyen Universtiy of Sciences, Thai Nguyen, Vietnam

DOI:

https://doi.org/10.15419/bmrat.v4iS.301

Abstract

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-transretinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of

cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs
in both intestinal and diffuse types of gastric carcinoma.

References

1. Nguyen, P.H., Giraud, J., Staedel, C., Chambonnier, L., Dubus, P., Chevret, E., Bœuf, H., Gauthereau, X., Rousseau, B., Fevre, M., et al. (2016). All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. Oncogene.
2. Nguyen, P.H., Giraud, J., Chambonnier, L., Dubus, P., Wittkop, L., Belleannée, G., Collet, D., Soubeyran, I., Evrard, S., Rousseau, B., et al. (2017). Characterization of Biomarkers of Tumorigenic and Chemoresistant Cancer Stem Cells in Human Gastric Carcinoma. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 23, 1586–1597.

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Published

2017-09-05

How to Cite

ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. (2017). Biomedical Research and Therapy, 4(S), S 98-99. https://doi.org/10.15419/bmrat.v4iS.301