UCLA

Prostatic adenocarcinomas can recur with aggressive and lethal small cell neuroendocrine carcinoma (SCNC). Since glycolysis is a feature of malignancy and the degree generally correlates with tumor aggressiveness, glucose metabolism and the molecular mechanisms involved between the two tumor types was studied. LNCaP and PC-3 cell lines modeled adenocarcinoma and SCNC, respectively, to compare glycolytic features and metabolomics. CD44’s role was studied by RNA knockdown and overexpression. Human tissue microarrays were analyzed for glycolytic enzyme expression. Glycolytic features were found to be higher in PC-3 over LNCaP cells. PFKFB4 was overexpressed in SCNC. CD44 regulated glucose metabolism, intracellular ROS, and cell proliferation in PC-3 cells. CD44 inhibition sensitized PC-3 cells to carboplatin. The data suggests different pathways of glucose metabolism may contribute to the differing biological behaviors of the two tumor types. CD44 was found to be an important regulator of glucose metabolism in SCNC and potential therapeutic target.