TGFβ1 in fibroblasts-derived exosomes promotes epithelial-mesenchymal transition of ovarian cancer cells
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Wenqian Li1, Xiaoxue Zhang1, Ji Wang1, Mengchen Li1, Canhui Cao1, Jiahong Tan1, Ding Ma1 and Qinglei Gao1
1Cancer Biology Research Center (Key Laboratory of The Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People’s Republic of China
Ding Ma, email: [email protected]
Qinglei Gao, email: [email protected]
Keywords: ovarian cancer; CAF; exosomes; TGFβ1; epithelial-mesenchymal transition
Received: May 09, 2017 Accepted: August 26, 2017 Published: October 06, 2017
Cancer-associated fibroblasts (CAF), a major component of the tumor microenvironment, play an important role in interacting with neoplastic cells to promote ovarian cancer progression. Exosomes are nano-sized vesicles that mediate the cross-talk between different cell types. An increasing number of studies have focused on the fact that tumor cell-derived exosomes influence stromal cells. However, the mechanism by which CAF-derived exosomes modulate cancer cells in ovarian cancer remains obscure. To investigate the role of CAF exosomes in ovarian cancer, we examined the exosomal content of paired primary, metastatic and normal fibroblasts from seven stage IIIC ovarian cancer patients by ELISA. We found that in ovarian CAF-derived exosomes, TGFβ1 was upregulated compared to normal omentum fibroblasts (NOF). Exosomes derived from CAF were taken up by ovarian SKOV-3 and CAOV-3 cell lines during co-culture and induced malignant behaviors in cancer cells, including an enhanced migration and invasion ability and the promotion of epithelial-mesenchymal transition (EMT) by activating the SMAD signaling pathway. Our results indicate that the role of TGFβ1 in CAF exosomes triggers ovarian cancer cells into a more aggressive phenotype, suggesting that targeting CAF exosomes could be a potential treatment in ovarian cancer.
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