HGF and IGF-1 synergize with SDF-1α in promoting migration of myeloma cells by cooperative activation of p21-activated kinase.

摘要: Stromal-derived factor (SDF)-1α, insulin-like growth (IGF)-1 and hepatocyte (HGF) are potent mediators of cell migration. We studied the effect combinations these cytokines on migration myeloma cells. When SDF-1α was combined with either HGF or IGF-1, we found a striking synergy in cytokines' ability to guide cells across transwell membrane. Between IGF-1 there no cooperativity. However, effects were not redundant. SDF-1 caused concentration gradient-directed migration, as opposed which apparently randomly directed movement. The SDF-1α-driven JJN-3 cells, line secreting large amounts HGF, reduced when given an inhibitor receptor, demonstrating cooperative activity between autocrine exogenous SDF-1α. There clear positive correlation degree cytokine-induced phosphorylation p21-activated kinase (PAK) both primary lines including INA-6 IH-1. Downregulation PAK small interfering RNA resulted decreased cytokine-driven This study shows HGF/IGF-1 inducing yet each cytokine has distinct properties way it regulates These findings likely be clinical relevance because multiple located environment containing exposed gradient bone marrow peripheral blood.