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Am J Cancer Res. 2018 Aug 1;8(8):1624-1632. eCollection 2018.

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

Xu N1, Li X2, Watanabe M1,3, Ueki H1, Hu H4, Li N4, Araki M1, Wada K1, Xu A2, Liu C2, Nasu Y1,3,5, Huang P1,2,5.

Author information

1
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama, Japan.
2
Department of Urology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
3
Center for Innovative Clinical Medicine, Okayama University Hospital Okayama, Japan.
4
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center Guangzhou, China.
5
Okayama Medical Innovation Center, Okayama University Okayama, Japan.

Abstract

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.

KEYWORDS:

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

PMID:
30210930
PMCID:
PMC6129491

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