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Role of Pyruvate kinase M2 (PKM2) in tumor growth, cancer cell migration and tumor angiogenesis
Introduction: The pyruvate kinase isoforms PKM1 and PKM2 are alternatively spliced products of the pkm2 gene. PKM2, but not PKM1, is expressed in highly proliferating cells such as embryonic cells and all cancer cells reported to date. PKM2 has been reported to alter glucose metabolism in cancer cells and to contribute to tumorigenesis by mechanisms that are not explained by its known biochemical activity.
Aim: The aim of this study was to investigate the implication of Pyruvate kinase M2 isoform in pancreas tumor growth and tumor angiogenesis.
Results: RNAi-mediated depletion of PKM2 in three independent human pancreatic cancer cell lines resulted in impaired proliferation and a markedly decreased chemotactic migration. Our in vivo tumor xenograft experiments conducted on chicken chorionallantoic membrane (CAM) reinforced the role of PKM2 in growth of cancer cells as demonstrated by a significant decrease in the number of Ki-67 positive tumor cells after siRNA-mediated ablation of the kinase. Furthermore, the examination of peritumoral blood vessel formation revealed that the reduction in tumor size was associated with a marked reduction in desmin and von Willebrand Factor VIII immunoreactivity both in vessels surrounding the tumor and within the tumor xenografts.
Conclusion: Collectively, these finding demonstrate the role of PKM2 as a critical regulator of tumor growth and tumor angiogenesis and it could provide a useful target for regulation of pathological blood vessel formation.