الفهرس | Only 14 pages are availabe for public view |
Abstract The expression pattern of syndecan-1(SDC-1) in Hepatocellular carcinoma (HCC) has been changed from normal sinusoidal to constant honeycomb-like membrane distribution. Angiotensin II (Ang II) was found to relate to liver fibrosis development. TGF-β1 is mainly derived from infiltrating monocytes and induces the progression of liver fibrosis. The present study aimed to investigate the interaction between hepatic cancer cells, fibroblasts, and monocytes in the presence of overexpressed SDC-1. The human hepatocellular carcinoma (Hep3B), Syndecan-1 transfected Hep3B (Hep3B-SDC-1), monocyte cell lines (U937 and Mono-Mac-6), and human hepatic stellate (LX2) cell lines were cultured in vitro. Secretomes were detected using the dot blot technique and cytokine array. The results showed alteration in secreted proteins, cytokines, chemokines, basal expression levels, and activation status of multiple signaling pathways of Hep3B-SDC-1 compared to vector cells. In addition to the alterations detected in various signaling pathways in monocytes cell lines upon stimulation with Secretome of Hep3B, Hep3B-SDC-1, and Lx2 cells. Ang II and TGFβ1 influence Lx2 cells. Significant decrease in AT-1 expression in cirrhotic liver tissue due to HCV was observed with significant elevation in SDC-1 in liver tissues with cirrhosis and HCC. In conclusion, the presented results suggest that SDC-1 overexpression induces specific alterations in tumor-microenvironment associated cells such as (fibroblasts and monocytes). Furthermore, the interaction of SDC-1 with Ang II and TGF-β has been revealed to induce a critical modulation in hepatic cancer cells and fibroblasts. |