Hypoxia-Inducible Factor-1α (HIF-1α) Promotes Hypoxia-Induced Invasion and Metastasis in Ovarian Cancer by Targeting Matrix Metallopeptidase 13 (MMP13)
Hui Zhang, Qingju Yang, Xuanye Lian, Ping Jiang, Jing Cui
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China (mainland)
Med Sci Monit 2019; 25:7202-7208
Available online: 2019-09-25
Hypoxia promotes cancer progression. Hypoxia-inducible factor-1alpha (HIF-1alpha) has been reported to enhance tumor invasion and metastasis via activating downstream genes, such as matrix metalloproteinases (MMPs). The purpose of this study was to explore the probable roles of HIF-1alpha and MMP13 in the invasion and metastasis of ovarian cancer under hypoxic conditions.
MATERIAL AND METHODS: The expression of HIF-1alpha and MMP13 protein were detected with immunohistochemistry staining in ovarian cancer tissues, metastatic lesions, and normal fallopian tissues. Ovarian cancer A2780 cells were cultured under normoxic condition and hypoxic condition. mRNA and protein expression of HIF-1alpha and MMP13 were detected by RT-PCR and Western blot analysis. The effects of siRNA against HIF-1alpha on MMP13 expression were examined by RT-PCR and Western blot analysis. Transwell invasion assays were performed to test the invasive ability of A2780 cells.
RESULTS: Immunohistochemistry staining showed significantly higher expression of HIF-1alpha and MMP13 protein in ovarian cancer tissues and metastatic lesions than in normal fallopian tissues. HIF-1alpha and MMP13 expression were closely related. After exposure to hypoxia, mRNA and protein levels of HIF-1alpha and MMP13 were upregulated. siRNA effectively inhibited HIF-1alpha expression and MMP13 expression. The number of invading A2780 cells decreased after HIF-1alpha was silenced.
CONCLUSIONS: This study suggests that HIF-1alpha promotes ovarian cancer cell invasion through a MMP13 mechanism. It might be an effective strategy targeting HIF-1alpha - MMP13 to inhibit invasion and metastasis of ovarian cancer.
Keywords: Cell Hypoxia, Neoplasm Metastasis