Nitric oxide induced by tumor cells activates tumor cell adhesion to endothelial cells and permeability of the endothelium in vitro.
Human fibrosarcoma HT1080 cell surface phenotype analysis revealed the expression of "cluster of differentiation 15" (CD15) antigen and to a lesser extent, of "very late antigen-4" (VLA-4). Expression of "endothelial-leukocyte adhesion molecule-1" (ELAM-1) was negligible on resting human umbilical vascular endothelial cells (HUVECs), but its expression could be induced by HT1080 conditioned medium. HT1080 cell adhesion to HUVECs was partially dependent on CD15/ELAM-1 adhesion molecules. HT1080 cell adhesion to HUVECs induced the enhancement of nitric oxide (NO) production from HUVECs. Exogenous NO and NO from HUVECs enhanced ELAM-1 expression on HUVECs, HT1080 cell adhesion to HUVECs, permeability of the HUVEC monolayer, and HT1080 cell invasion through the HUVEC monolayer. These enhancements were not induced by NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). These results suggest that NO expression induced by tumor cells via the CD15/ELAM-1 adhesion system may contribute to enhancement of tumor cell adhesion to endothelial cells and hyperpermeability of the endothelium, facilitating tumor cell invasion.
Yudoh
K
K
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan. yudo3817@ms.toyama-mpu.or.jp
Matsui
H
H
Tsuji
H
H
D002199:Capillary Permeability; D002448:Cell Adhesion; D017077:Culture Media, Conditioned; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005354:Fibrosarcoma / Q000473:pathology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D009569:Nitric Oxide / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D019040:E-Selectin; D039041:Integrin alpha4beta1; D016023:Integrins; D016256:Lewis X Antigen; D016201:Receptors, Lymphocyte Homing; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester