Cooperative Interactions of Laminin 5 γ2 Chain, Matrix Metalloproteinase-2, and Membrane Type-1-Matrix/Metalloproteinase Are Required for Mimicry of Embryonic Vasculogenesis by Aggressive Melanoma

摘要: Vasculogenic mimicry describes a process where aggressive tumor cells in three-dimensional matrices mimic embryonic vasculogenesis by forming extracellular matrix (ECM)-rich, patterned tubular networks. Microarray gene chip analyses revealed significant increases the expression of laminin 5 (Ln-5, gamma2 chain) and metalloproteinases (MMP)-1, -2, -9, MT1-MMP (MMP-14) compared with poorly melanoma cells. These components colocalized developing networks antisense oligonucleotides to Ln-5 chain (but not sense oligonucleotides), antibodies MMP-2 or MMP-9) inhibited formation these Cultures which did receive either MMPs-2 -14 contained promigratory cleavage fragments. Poorly seeded on collagen I preconditioned formed along chain-enriched tracks deposited results suggest that increased MT1-MMP, deposition and/or its fragments, are required for vasculogenic Furthermore, apparent recapitulation laminin-rich, observed patients' tissue sections culture may also serve as model help identify specific molecular targets could function templates coordinated migration their proteolytic remodeling ECM have profound implications development novel therapies directed at alter progression.