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Abstract
This Podcast features an interview with Yuichi Oike, author of a Research Article that appears in the 21 January 2014 issue of Science Signaling, about how the tumor microenvironment affects the aggressiveness of osteosarcoma cells through a secreted factor called angiopoietin-like protein 2 (ANGPTL2). As tumors grow, the tumor microenvironment becomes depleted of oxygen and nutrients, which limits further growth of the tumor. Cancer cells may then metastasize, leaving the primary tumor and colonizing a secondary site where growth conditions are favorable. Odagiri et al. investigated how the tumor microenvironment influences expression of ANGPTL2, which has been implicated in metastasis. The authors found that hypoxic, nutrient-limited growth conditions stimulated the expression of ANGPTL2 by promoting demethylation of the ANGPTL2 promoter. Increased expression of ANGPTL2 correlated with increased metastasis of osteosarcoma cells grown as xenografts in mice and inversely correlated with human osteosarcoma patient survival. ANGPTL2 was cleaved into inactive fragments by tolloid-like 1 (TLL1), which is a protease that was not abundant in human osteosarcoma samples. Thus, increasing the abundance or activity of TLL1 may be a useful strategy for decreasing the likelihood of metastasis in osteosarcoma patients.
