Hypoxia Increases the Proliferative and Metastatic Ability of Canine Mammary Tumor Cells via Up-regulation of TSG-6

초록

Background/Aim: HIF1 alpha-induced hypoxia is a major characteristic of solid tumors that plays an important role in cancer growth, metastasis, and chronic inflammation. Tumor necrosis factor (TNF) stimulated gene (TSG)-6 is a strong regulator of anti-inflammatory pathways, but its role in cancer cells remains unclear. We hypothesized that hypoxia upregulates TSG-6, thereby increasing the metastatic and growth potential of cancer cells. Materials and Methods: Primary and metastatic canine mammary gland tumor (MGT) cell lines (CIPp and CIPm), were transfected with TSG-6 specific siRNA and treated with cobalt chloride (CoCl2) for 48 h to chemically induce a hypoxia environment. The expression of hypoxiainducible factor-1-alpha (HIF1 alpha) was evaluated by RT-qPCR and western blot analysis. The metastatic ability of cancer cells and cell cycle distribution were assessed with extracellular matrix invasion assays and flow cytometry. Results: HIF1 alpha upregulation, induced by CoCl2, was significantly inhibited in the TSG-6-knockdown group in both canine MGT cell lines. The change in the expression levels of HIF1 alpha corresponded to the change of invading cells in the TSG-6-knockdown group. TSG6-knockdown in the hypoxia group showed decreased proliferation, associated with G2/M phase arrest. Conclusion: HIF1 alpha expression in hypoxic condition is regulated by TSG-6

키워드