Leukocyte recruitment in colon cancer: role of cell adhesion molecules, nitric oxide, and transforming growth factor beta1

Gastroenterology
Xavier BessaAntoni Castells

Abstract

A deficient leukocyte recruitment has been suggested in tumor vasculature, but little is known about the underlying molecular mechanism. To characterize leukocyte-endothelium interaction in experimental colon cancer, quantify the main endothelial cell adhesion molecules (CAMs), and evaluate the effect of tumor-derived products. Leukocyte recruitment was assessed by intravital videomicroscopy in mice bearing HT29-derived tumors. Endothelial CAMs were measured using the dual-radiolabeled antibody technique. The role of molecules mediating leukocyte rolling (P-, E-, and L-selectin) or adhesion (intercellular adhesion molecule 1 [ICAM-1] and vascular cell adhesion molecule 1 [VCAM-1]) carcinoembryonic antigen (CEA), and transforming growth factor (TGF) beta1 was assessed through immunoblockade, whereas participation of nitric oxide (NO) and cyclooxygenase (COX) metabolites were evaluated by means of nonselective and selective inhibition. Basal and lipopolysaccharide-stimulated leukocyte rolling and adhesion were markedly reduced in tumor vasculature. ICAM-1 immunoblockade prevented leukocyte adhesion in both tumor and nontumor microvessels. Neither baseline nor LPS-induced endothelial ICAM-1, P-, and E-selectin expression in tumors...Continue Reading

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