Overexpression of CD147 in ovarian cancer is initiated by the hypoxic microenvironment.

Ovarian cancer is a lethal malignant tumour characterised by activated invasion, distant metastasis, anti-cancer drug resistance, angiogenesis and metabolism. CD147, an extracellular matrix metalloproteinase inducer, is overexpressed in most ovarian tumours and plays an important role in the progression of ovarian cancer and other malignant tumours. However, the factor(s) initiating this overexpression is unknown. Because of rapid reproduction and their hypoxic microenvironment, malignant tumours use glycolysis for energy, and lactic acid produced is harmful to the cells. For survival, excessive lactate needs to be transported by monocarboxylate transporters (MCTs). Functioning of MCT1 and MCT4 require the ancillary of CD147. The gene for CD147 possesses two hypoxia-inducible factors binding sites in its 3'-flank. It is logical to postulate that the hypoxic microenvironment is a major initiator of the overexpression of CD147, thus conferring on ovarian cancers their malignant properties. A model that can represent spontaneous ovarian cancer is necessary to verify this hypothesis.