Pyruvate kinase M2 in blood circulation facilitates tumor growth by promoting angiogenesis

Abstract

It is long known that pyruvate kinase isoform M2 (PKM2) is released into the circulation of cancer patients. ThePKM2levels in patients have been suggested as a diagnostic marker for many types of cancers. However, it is not known howPKM2is released in the blood, and whether the circulating PKM2 has any physiological function(s) in tumor progression. In this report, we demonstrate thatPKM2in the blood facilitates tumor growth by promoting tumor angiogenesis. Our experiments show that PKM2 promotes tumor angiogenesis by increasing endothelial cell proliferation, migration, and cell-ECM adhesion. Only the dimeric PKM2 possess the activity in promoting tumor angiogenesis, which is consistent with the observations that PKM2 in circulation of cancer patients is a dimer form.