Abstract 3412: Hypoxia induces EMT in primary melanoma and MET in metastatic melanoma

Abstract

Abstract A low oxygen microenvironment (hypoxia) is observed in the skin and in solid tumors. In several different types of cancers hypoxia has been shown to induce primary tumor cell migration and cancer metastasis. Epithelial to mesenchymal transition (EMT) is an important process involving the transition of primary tumor cells to mobile metastatic tumor cells. Hypoxia has been reported to induce EMT in breast and ovarian cancers. However, little is known about the settlement process after metastatic tumor cells reach the distant metastatic site. In this study, we compared the effect of hypoxia on several primary and metastatic melanoma cell lines in cell morphology and cell motility. We observed different expression patterns of cell surface markers and transcription factors regulated by hypoxia that are important for the EMT process between primary and metastatic tumor cells. While hypoxia induces the expression of EMT markers in primary melanoma, it represses the expression of these markers as well as cell migration in metastatic melanomas. Furthermore, cell migration induced by hypoxia in primary melanoma cell is blocked by either HIF1α or HIF2α knock down. Cell migration repressed by hypoxia is reversed by knocking down HIF1α but not HIF2α in metastatic tumor cells. We propose that depending on the state of tumor progression, hypoxia can induce EMT in primary melanomas and MET in metastatic melanomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2011-3412