Effects of increased ambient pressure on colon cancer cell adhesion

Forces such as strain modulate intestinal epithelial biology. Shear and pre ssure influence other cells. The effects of pressure on human colon cancer cells are poorly understood. Increasing ambient pressure for 30 min by 15 m m Hg over atmospheric stimulated adhesion to matrix proteins of four human colon cancer cell lines and primary cells from three human colon cancers, b ut not bovine aortic smooth-muscle cells. Th is effect was energy dependent and cation dependent (blocked by azide and chelation), accompanied by tyro sine phosphorylation of intracellular proteins including focal adhesion kin ase, and blocked by tyrosine kinase inhibition (genistein, tyrphostin, and erbstatin) and a functional antibody to the pi integrin subunit. Although p ressure stimulated adhesion even in a balanced salt solution, baseline and pressure-stimulated adhesion were each substantially diminished in the abse nce of serum. These data suggest that relatively low levels of increased pr essure may stimulate malignant colonocyte adhesion by a cation-dependent pl -integrin-mediated mechanism, perhaps via focal adhesion kinase-related tyr osine phosphorylation. In addition to elucidating another aspect of physica l force regulation of colonocyte biology, these findings may be relevant to the Effects of increased pressure engendered by colonic peristalsis, surgi cal manipulation, or laparoscopic surgery on colon cancer cell adhesion. (C ) 2000 Wiley-Liss, Inc.