Directional Migration of Melanoma Cells On Post Gradient Density Arrays

Melanoma encounters severed extracellular matrix (ECM) by proteolysis and initiates metastasis. During this process, the inhomogeneous texture of in vivo ECM architecture is exposed and this affects cell migration. We investigate melanoma cell migration on this inhomogeneity with post gradient density array (GPDA). Malignant melanoma, 1205Lu migrates from denser to sparser post arrays preferentially to higher ECM contact by more wrapping posts on sparser than denser arrays. This directional migration is reversed by the inhibition of PI3K activity to control the protrusion of infiltration. Moreover, the biased translocations of PI3K toward sparser post array and, in turn, reduced intercellular tensions on sparser zone of GPDA are consistent with the directions of 1205Lu migration. Conversely, benign melanoma, Scbl2 that have less PI3K activity exhibits the reversed migration on high ECM density coated GPDA. Reduced PI3K activity induces the enhancement of intercellular tension by increased MLCK, which impede the vertical protrusion of pseudopods for cells to confine the top of posts. This allows cells to contact more area from denser post arrays, which cause translocation of PI3K toward denser arrays and, thus, increased intercellular tension on sparser ones. This reversed migration of Scbl2 on GPDA is re-reversed by the inhibition of MLCK. These data demonstrate PI3K determines distinctive directional migrations of melanoma cells on inhomogeneous ECM structure in metastasis.