Effects of increased ambient pressure on colon cancer cell adhesion

Abstract

Forces such as strain modulate intestinal epithelial biology. Shear and pressure influence other cells. The effects of pressure on human colon cancer cells are poorly understood. Increasing ambient pressure for 30 min by 15 mm Hg over atmospheric stimulated adhesion to matrix proteins of four human colon cancer cell lines and primary cells from three human colon cancers, but not bovine aortic smooth-muscle cells. This effect was energy dependent and cation dependent (blocked by azide and chelation), accompanied by tyrosine phosphorylation of intra-cellular proteins including focal adhesion kinase, and blocked by tyrosine kinase inhibition (genistein, tyrphostin, and erbstatin) and a functional antibody to the β integrin subunit. Although pressure stimulated adhesion even in a balanced salt solution, baseline and pressure-stimulated adhesion were each substantially diminished in the absence of serum. These data suggest that relatively low levels of increased pressure may stimulate malignant colonocyte adhesion by a cation-dependent β1-integrin-mediated mechanism, perhaps via focal adhesion kinase-related tyrosine phosphorylation. In addition to elucidating another aspect of physical force regulation of colonocyte biology, these findings may be relevant to the effects of increased pressure engendered by colonic peristalsis, surgical manipulation, or laparoscopic surgery on colon cancer cell adhesion. (C) 2000 Wiley-Liss, Inc.