The differential effect of endothelial cell factors on in vitro motility of metastatic and non metastatic cells

Motility of tumor cells plays a critical role in tumor metastasis, and as such is a target for intervention. The motility of Calu-1 epithelial lung carcinoma cells is upregulated when placed in co-culture with human umbilical vein endothelial cells (HUVECs), while that of nonmetastatic L132 lung epithelial cells is not. In order to determine the major factor(s) causing these changes in epithelial cell motility, the motile response of both cell types to HUVEC secreted factors-soluble, on the HUVECs themselves, and secreted to the exuacellular matrix (ECM)-and to individual ECM proteins was measured by obtaining cell track data with time-lapse videomicroscopy and fitting it to a persistent random walk model of motility. None of the factors tested had a large up-regulatory effect on L132 cell motility, but the Calu-1 cell motility was up-regulated by the HUVEC secreted ECM, and was up-regulated differentially by the individual ECM proteins tested. Flow cytometry analysis showed that the expression levels of the integrin subunits β1, α2, and α6 are significantly higher on the Calu-1 cells than on the L132 cells, implicating a role for integrins in the observed motile behaviors of these cell lines