Model for the

ménage a trois between syndecan-1, Met, and HGF in MM. Syndecan-1 may promote Met signaling by several mechanisms. First, binding of autocrine or paracrine (bone marrow stroma) produced HGF by the HS side chains of syndecan-1 may result in dimerization or oligomerization of HGF, thereby promoting Met cross-linking and tyrosine kinase activity (1). Second, HGF and syndecan-1 interaction might induce a conformational change of HGF, leading to enhanced signal transduction (2). Third, HGF may mediate colocalization of syndecan-1 and Met. Ternary complex formation between HGF, Met, and syndecan-1 may bring relevant intracellular signaling molecules together, which may facilitate their activation by Met (3). See “Discussion” for further detail.