Role of midkine-progranulin interaction during angiogenesis of hepatocellular carcinoma.

Midkine (MK) is a heparin-binding growth factor involved in growth, survival, migration, and differentiation of various target cells and dysregulation of MK signaling is implicated in a variety of inflammatory diseases and cancers. Although MK has been reported to act on endothelial cells and to have proangiogenic effects, the exact role of MK in angiogenesis is poorly defined. Progranulin (PGRN) is a secreted glycoprotein that functions as an important regulator of development, cell cycle progression, cell motility, tumorigenesis, angiogenesis. We screened the PGRN from the hepatic cancer cell cDNA library which was interacted with MK, and confirmed the binding by co-immunoprecipitation and co-localization. During our study, the interaction between MK and PGRN had the important role on the HUVECs proliferation, migration, and tubulogenesis, which indicated the interaction may regulate the angiogenesis, also the in vivo angiogenesis model CAM showed the promotion effect stimulated by MK and PGRN. These findings provide the first evidence linking the association of MK and PGRN and may identify the mechanism of MK during the hepatocellular carcinoma angiogenesis.