Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer
Pancreatic cancer-derived exosomes promoted pancreatic stellate cells recruitment by pancreatic cancer
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胰腺癌来源的外泌体促进胰腺癌招募胰腺星状细胞
DOI：
10.7150/jca.27590
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发表时间：
2019-07
影响因子：
3.9
通讯作者：
Yu-Lian Wu
中科院分区：
文献类型：
--
作者：
Yue-Feng Zhang;Yi-Zhao Zhou;Bo Zhang;Shi-Fei Huang;Peng-Ping Li;Xiao-Man He;Guo-Dong Cao;Mu-Xing Kang;Xin Dong;Yu-Lian Wu
癌症相关成纤维细胞（CAF）是肿瘤微环境的重要组成部分，已在癌症转移患者的血液循环中发现，转移性癌细胞可以招募循环CAF。然而，原发癌部位通常通过外泌体调节转移癌细胞的行为。在这里，我们假设癌症来源的外泌体可以增强CAF募集。分离并表征由胰腺癌细胞（PANC-1和MIA PaCa-2）分泌的外泌体。通过体外Transwell实验和体内小鼠模型生物发光成像评估胰腺癌募集胰腺星状细胞（PSC）的能力，并研究其潜在的分子机制。结果表明，胰腺癌细胞来源的exosomes（Exo-Pan和Exo-Mia）促进胰腺癌PSC的募集。这种作用部分通过将外泌体蛋白Lin 28 B转移到受体细胞以激活Lin 28 B/let-7/HMGA 2/PDGFB信号通路来介导。这些结果表明，来源于局部癌症的外泌体可以通过将外泌体蛋白Lin 28 B转移到转移癌细胞来促进远处转移的形成。
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.
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