CXCL1 mediates adiponectin-induced angiogenesis in ovarian cancer

초록

Objective: Adiponectin is a cytokine secreted from adipose tissue that regulates energy homeostasis, inflammation, and cell proliferation. Obesity is associated with increased risk of various cancers, including ovarian cancer. Adipokines, including adiponectin, have been implicated as a factor linking obesity and carcinogenesis. The oncogenic role of adiponectin is not known with regard to various cancer types. We sought to determine the role of adiponectin in angiogenesis in ovarian cancer in vitro. Method: We transfected SKOV3 cells with vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) in order to identify the independent angiogenic role of adiponectin in ovarian cancer. The VEGF-knockdown SKOV3 cell lines were treated with adiponectin for 48 hours. The cytokines involved in adiponectin-mediated angiogenesis were explored using the human angiogenesis cytokine array and were verified with the enzyme-linked immunosorbent assay. The angiogenic effect of adiponectin was evaluated using the human umbilical vein endothelial cell (HUVEC) tube formation assay. We also investigated the effects of adiponectin treatment on the migration and invasion of SKOV3 cells. Results: The number of tubes formed by HUVEC decreased significantly after knockdown of VEGF (via transfection of VEGF siRNA into SKOV3 cells). When these VEGF-knockdown SKOV3 cells were treated with adiponectin, there was an increase in the number of tubes in a tube formation assay. Following adiponectin treatment, the CXC chemokine ligand 1 (CXCL1) secretion increased in a cytokine array. This was confirmed by both enzyme-linked immunosorbent assay and Western blot. The increased secretion of CXCL1 by adiponectin occurred regardless of VEGF-knockdown. In addition, the induction of migration and invasion of SKOV3 cells were significantly stronger with adiponectin treatment than they were without. Conclusion: Adiponectin treatment of ovarian cancer cells induces angiogenesis via CXCL1 independently of VEGF. These findings suggest that adiponectin may serve as a novel therapeutic target for ovarian cancer.