J Cancer 2018; 9(3):614-628. doi:10.7150/jca.19614
The role of cancer-associated fibroblast MRC-5 in pancreatic cancer
1. Shulan (Hangzhou) Hospital (Zhejiang University International Hospital), Hangzhou, Zhejiang, P.R. China
2. Division of oncology department, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
3. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health; Key Laboratory of Organ Trans-plantation, Zhejiang Province; Hangzhou, Zhejiang, China
4. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
Ding SM, Lu AL, Zhang W, Zhou L, Xie HY, Zheng SS, Li QY. The role of cancer-associated fibroblast MRC-5 in pancreatic cancer. J Cancer 2018; 9(3):614-628. doi:10.7150/jca.19614. Available from http://www.jcancer.org/v09p0614.htm
Background: Our previous study showed that cancer-associated fibroblast MRC-5 promoted hepatocellular carcinoma progression by enhancing migration and invasion capability. However, few studies have explored the role of MRC-5 in pancreatic cancer (PC). In this study, we examined the exact role and associated mechanisms of MRC-5.
Methods: The conditioned media for MRC-5 was used to culture PC cell lines SW1990 and PANC-1. Cell proliferation was compared based on colony formation assays of PC cells in normal media and of PC cells cultured with conditioned media of MRC-5. Cell migration and invasion were assayed by transwell chambers. The expression of EMT-related proteins and apoptosis-related proteins was evaluated using Western blot. And confocal microscopy was used to further detect the expression of EMT-related proteins. qRT-PCR was used to confirm the expression changes of related genes at the mRNA level. We also used flow cytometry to examine the cell cycle, apoptotic rate, and expression of CD3, CD4, CD14, CD25, CD45, CD61, CD90, TLR1, and TLR4.
Results: MRC-5 repressed the colony formation ability of PC cells and significantly inhibited cell migration and invasion potential. MRC-5 induced S-phase cell cycle arrest but did not augment the apoptotic effects in PC cells. We hypothesized that the weakened malignant biological behavior of PC cells was correlated with MRC-5-induced altered expression of the cancer stem cell marker CD90; the immune-related cell surface molecules CD14, CD25, TLR4, and TLR1; and cell polarity complexes Par, Scribble, and Crumbs.
Conclusion: MRC-5 limits the malignant activities of PC cells by suppressing cancer stem cell expansion, remolding epithelial polarity, and blocking the protumoral cascade reaction coupled to TLR4, TLR1, CD14, and CD25.
Keywords: Cancer associated fibroblast (CAF), Cancer stem cell (CSC), Toll-like receptors (TLRs), Epithelial-to-mesenchymal transition (EMT), Cell polarity complex