Pancreatic cancer‐secreted miR‐155 implicates in the conversion from normal fibroblasts to cancer‐associated fibroblasts

Cancer Science

Wenjing Pang¹  Jiaojiao Su²  Yalei Wang²  Hui Feng²  Xin Dai¹  Yaozong Yuan¹  Xi Chen³ 

[1] Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China;Department of Gastroenterology, First-affiliated Hospital, Anhui Medical School, Hefei, China;Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical, Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

关键词: Cancer‐associated fibroblast;    microRNA;    microvesicle;    pancreatic neoplasm;    tumor microenvironment;   

DOI  :  10.1111/cas.12747

来源: Wiley

【 摘 要 】

Abstract

Cancer-associated fibroblasts (CAF) are a major constituent of the pancreatic cancer microenvironment and that the meaning is as intended. Pancreatic cancer cells can induce normal fibroblasts to convert into CAF and, reciprocally, CAF promote tumor invasions and proliferations. The mechanism of the conversion from normal fibroblasts (NF) to CAF remains unclear. MicroRNA are short non-coding RNA involved in the post-transcription gene regulation, which have been defined as an imperative controller in tumor invasions, proliferations and colony formations. Microvesicles (MV) have been proved to be an important mediator of intercellular communication and can selectively transport secreted microRNA from a donor cell into a recipient cell. In this study, we isolated primary pancreatic fibroblasts from wild type C57 mice and co-cultured them with pancreatic cancer cell lines, BxPC-3 and SW1990, and observed the conversion from NF to CAF, or at least CAF-like cells. This phenomenon could also be replicated in primary fibroblasts treated with MV separated from a cancer cell media. We identified that miR-155 was upregulated in PaC-derived MV and we confirmed that normal fibroblasts could convert into CAF after MV containing miR-155 had been taken up. TP53INP1 is a target of miR-155 in fibroblasts and a downregulation of TP53INP1 protein levels could contribute to the fibroblasts' activation. These results indicated that pancreatic cancer cells might reprogram normal adjacent fibroblasts into CAF by means of secreted MV containing miR-155. Targeting the circulating microRNA might be a potential therapy for malignant tumors.

【 授权许可】

CC BY-NC-ND   
© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.