Induction of cells with prostate cancer stem-like properties from mouse induced pluripotent stem cells via conditioned medium

American Journal of Cancer Research

Masami Watanabe¹  Naijin Xu²  Xiezhao Li³  Hideo Ueki⁴  Hao Hu⁵ 

[1] Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan;Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan;Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China;Guangzhou Institute of Pediatrics, Guangzhou Women and Childrens Medical Center, Guangzhou, China;Okayama Medical Innovation Center, Okayama University, Okayama, Japan

关键词: Induced pluripotent stem cell;    prostate cancer;    cancer stem cell;    conditioned medium;    tumor microenvironment;    chemoresistance;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

Cancer stem cells (CSCs) that closely correlated with tumor growth, metastasis, provide a plausible explanation for chemoresistance and cancer relapse. CSCs are usually isolated and enriched from carcinoma cells, which is inconvenient, low-efficient, and even unreliable. Here, we converted mouse induced pluripotent stem cells (miPSCs) into prostate cancer stem-like cells with carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9, a mouse prostate cancer cell line. These transformed cells, termed as miPS-RM9CM, displayed CSCs properties, including spheroids morphology and expression of both stemness genes and cancer stem cells surface markers, such as Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44, and CD133. In addition, in vivo transplantation experiment was performed to confirm the tumorigenicity. Furthermore, we used the model to assess conventional chemotherapeutic agent, docetaxel. The results showed that miPS-RM9CM cells exhibited increased resistance to docetaxel, however, high susceptibility to the cancer cell stemness inhibitor I (BBI-608). Our current study demonstrates that CM from cultured RM9 cells play a crucial role in the determination of cell fate from miPSCs to cancer stem-like cells and provide a potentially valuable system for the study of CSCs.

【 授权许可】

CC BY-NC