J Cancer 2019; 10(18):4397-4407. doi:10.7150/jca.27590

Research Paper

Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer

Yue-Feng Zhang5, Yi-Zhao Zhou1,2, Bo Zhang1, Shi-Fei Huang3, Peng-Ping Li1,2, Xiao-Man He1,2, Guo-Dong Cao1,2, Mu-Xing Kang1,2, Xin Dong1,4, Yu-Lian Wu1✉

1. Department of Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
2. Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China.
3. Department of Surgery, Traditional Chinese Medical Hospital of Hangzhou, Hangzhou, Zhejiang, P.R. China.
4. Department of General Surgery, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, P.R. China.
5. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China.

Abstract

Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been identified in the blood circulation of patients with cancer metastasis, and metastatic cancer cells can recruit circulating CAFs. However, primary carcinoma sites usually regulate the behavior of metastatic cancer cells through exosomes. Here, we hypothesized that cancer-derived exosomes could enhance CAF recruitment. Exosomes secreted by pancreatic cancer cells (PANC-1 and MIA PaCa-2) were isolated and characterized. The ability of pancreatic cancer to recruit pancreatic stellate cells (PSCs) was assessed with Transwell assays in vitro and bioluminescent imaging in a mouse model in vivo, and the underlying molecular mechanism was also investigated. The results showed that pancreatic cancer cell-derived exosomes (Exo-Pan and Exo-Mia) promoted the pancreatic cancer recruitment of PSCs. This effect was mediated partially by the transfer of the exosomal protein Lin28B to the recipient cells to activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway. These results suggested that exosomes derived from local cancer could promote the formation of distant metastases through transferring the exosomal protein Lin28B to the metastatic cancer cells.

Keywords: Pancreatic cancer, Pancreatic stellate cells (PSCs), Exosomes, Recruitment

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How to cite this article:
Zhang YF, Zhou YZ, Zhang B, Huang SF, Li PP, He XM, Cao GD, Kang MX, Dong X, Wu YL. Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer. J Cancer 2019; 10(18):4397-4407. doi:10.7150/jca.27590. Available from http://www.jcancer.org/v10p4397.htm