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MP41-12: INDUCTION OF PROSTATE CANCER STEM CELL PROPERTIES IN MOUSE INDUCED PLURIPOTENT STEM CELLS VIA DEFINED CARCINOMA NICHE AND TRACKING DRUG RESPONSE IN PRECLINICAL RESEARCH

Saturday, May 13
3:30 PM - 5:30 PM
Location: BCEC: Room 156

Presentation Authors: Naijin Xu*, Okayama, Japan, Xiezhao Li, Aibai Xu, Guangzhou, China, People's Republic of, Masami Watanabe, Okayama, Japan, Peng Huang, Guangzhou, China, People's Republic of, Yasutomo Nasu, Okayama, Japan, Chunxiao Liu, Guangzhou, China, People's Republic of

Introduction: Cancer stem cells (CSCs), that closely correlated with tumor growth, metastasis and provide a plausible explanation for chemoresistance and cancer relapse. CSCs were isolated and enriched from carcinoma cells usually, which were inconvenient, low-efficient, and even unreliable. The purpose of this study was to establish prostate CSCs converted from mouse induced pluripotent stem (iPS) cells, that would allow us to monitoring tumor progression and tracking novel drug response.

Methods: We converted mouse iPS cells into prostate CSCs with defined carcinoma microenvironment following exposure to conditioned medium (CM) derived from RM9-KLK3, a mouse prostate cancer cell line encoded by human KLK3/PSA gene. We also evaluated the expression of various stemness genes and cancer stem cell surface markers, including Oct3/4, Sox2, Nanog, Klf-4, c-Myc, CD44 and CD133, accompanied with the prostate special antigen (PSA) in these cells. In addition, in vivo transplantation experiment was performed to confirmed the tumorigenicity. Furthermore, we used these model on assess new drug response.

Results: These induction CSCs expressed embryonic stem cell markers, accompanied by significantly elevated expression of CSCs surface markers and PSA. Moreover, after subcutaneous injection into C57BL/6 mice, these cells displayed high tumorigenicity. The tumor derived from CSCs exhibited malignant phenotype and showed high expression of Ki-67 and CD31. We also confirmed that novel drug, such as cancer stemness inhibitor suppressed these induction cells significantly compared to the chemotherapy (in vitro and in vivo assay). RT-PCR and Western blot analysis suggested the possible mechanism underlying this effect was dependent on suppressing cancer stemness.

Conclusions: An efficient approach to enrich CSCs is extremely important for advancing cancer research. In current study, we converted mouse iPS cells into prostate CSCs with defined carcinoma niche. It is noteworthy that these induction CSCs model displayed stemness accompanied by high tumorigenicity, which could help design better agent for cancer therapeutic and suppress cancer relapse.

Source Of Funding: An efficient approach to enrich CSCs is extremely important for advancing cancer research. In current study, we converted mouse iPS cells into prostate CSCs with defined carcinoma niche. It is noteworthy that these induction CSCs model displayed stemness

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MP41-12: INDUCTION OF PROSTATE CANCER STEM CELL PROPERTIES IN MOUSE INDUCED PLURIPOTENT STEM CELLS VIA DEFINED CARCINOMA NICHE AND TRACKING DRUG RESPONSE IN PRECLINICAL RESEARCH



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