作者: Stefano Martinotti , Cora A. Damen , Gerard Groenewegen , Arjan W. Griffioen , Geert H. Blijham
DOI:
关键词:
摘要: Intercellular adhesion molecule 1 (ICAM-1) is involved in the recirculation of blood leukocytes and, presumably, infiltration cytolytic effector into tumors. The present report describes a down-regulated expression vascular ICAM-1 on tumor-infiltrating endothelial cells (EC) renal cell carcinoma. This finding was obtained by flow cytometric analysis tumor EC compared to from healthy tissue. Since growth solid tumors dependent formation new vessels (angiogenesis), we hypothesized that angiogenic factors are responsible for down-regulation ICAM-1. hypothesis investigated vitro using human umbilical vein- and dermis-derived EC. Using cytometry, found biphasic regulation during stimulation cultured with agent basic fibroblast factor (bFGF). Although 16-24 h after activation marked up-regulation observed, significantly decreased 48h. longevity this at least 7 days. Northern blot revealed steady-state mRNA level gene. ICAM-2 showed similar results intial up- later down-regulation. Functional relevance changes demonstrated corresponding EC-leukocyte bFGF. described effects specific bFGF since other (such as factor, transforming beta, interleukin 8) did not affect expression. Subsequent experiments decrease sensitivity necrosis factor-alpha regard reveal tumor-derived escape mechanism molecules vivo responsiveness proinflammatory cytokines.