MRC-5 fibroblast-conditioned medium influences multiple pathways regulating invasion, migration, proliferation, and apoptosis in XXXX .

@entity1 @entity8945 @entity0 @entity4245 @entity1476 @entity5 @entity588 @entity5962 @entity8780 @entity189 @entity18075 @entity3818 @entity157 @entity18436 @entity6076
BACKGROUND: @entity189 associated fibroblasts (CAFs), an important component of @entity5 microenvironment, are capable of enhancing @entity5 cells invasion and migration through initiation of epithelial-mesenchymal transition (EMT). MRC-5 fibroblasts are one of the CAFs expressing alpha-smooth muscle actin. It is ascertained that medium conditioned by MRC-5 fibroblasts stimulate motility and invasion of @entity0 cells. However, its role in @entity157 ( @entity157 ) is less clear. The aim of our study was to investigate the effect of MRC-5-CM on @entity157 and explore the underlying mechanisms. METHODS AND RESULTS: Using a combination of techniques, the role of MRC-5-CM in @entity157 was evaluated. We determined that MRC-5-CM induced the non-classical EMT in Bel-7402 and MHCC- @entity1 cell lines. Initiation of the non-classical EMT was mainly via quintessential redistribution of a-, b- and y-catenin, @entity8780 , @entity5962 , and @entity6076 , rather than up-regulation of typical EMT-related transcription factors (i.e., @entity4245 , @entity8945 , @entity18075 and @entity18436 ). We also found that MRC-5-CM potentiated both the migration and invasion of Bel-7402 and MHCC- @entity1 cells in mesenchymal movement mode through activation of the a6, b3, b4, b7 integrin/ @entity3818 pathway and upregulation of @entity1476 . The flow cytometric analysis showed that MRC-5-CM induced G1 phase arrest in Bel-7402 cells with a concomitant reduction of S phase cells. In contrast, MRC-5-CM induced S phase arrest in MHCC- @entity1 cells with a concomitant reduction of cells in the G2/M phase. MRC-5-CM also inhibited apoptosis in Bel-7402 cells while inducing apoptosis in MHCC- @entity1 cells. CONCLUSION: Collectively, MRC-5-CM promoted @entity157 cell motility and invasiveness through initiation of the non-classical EMT, including redistribution of a-, b- and y-catenin, @entity8780 , @entity5962 , and @entity6076 , activation of the integrin/ @entity3818 pathway, and upregulation of @entity1476 . Hence, MRC-5-CM exerted distinct roles in Bel-7402 and MHCC- @entity1 cell viability by regulating cyclins, cyclin dependent kinases (CDKs), CDK inhibitors (CKIs), @entity588 family proteins and other unknown mechanosensors.
