IDENTIFICATION OF 4 GENES IN ENDOTHELIAL-CELLS WHOSE EXPRESSION IS AFFECTED BY TUMOR-CELLS AND HOST IMMUNE STATUS - A STUDY IN EX VIVO-ISOLATED ENDOTHELIAL-CELLS

A spontaneously metastasizing, well-defined mouse lymphoma was chosen as an in vivo model to study the effect of tumor-host interaction on g ene expression in liver sinusoidal endothelial cells. Forty-nine bovin e aortic endothelial cell (BAEC) genes, recently isolated by a differe ntial screening approach of a cDNA library enriched for tumor necrosis factor-alpha (TNF-alpha) suppressed genes, were investigated. Four of these genes were finally selected because they were affected differen tially by host immune-competence, TNF-alpha, and tumor cells. Sequence analysis showed them to encode the bovine polyubiquitin (A4), elongat ion factor 1 alpha (B2), the acidic ribosomal phosphoprotein PO (C3), and the ribosomal protein S2 (E10). Gene expression was analyzed by do t-blot or Northern blot analysis. TNF-alpha and tumor cell conditioned supernatant suppressed the genes additive in BAEC but not in other en dothelial cells except for bovine capillary endothelial cells. Ex vivo -isolated liver endothelial cells of tumor-bearing syngeneic DBA/2 mic e showed strong downregulation of these four genes in comparison to no rmal control values. In contrast, endothelial cells of tumor-bearing i mmune-incompetent Balb/c (nu/nu) mice showed no downregulation but upr egulation of these genes. Consistently, all four genes were also downr egulated when BAEC were incubated with supernatants derived from ex vi vo-isolated liver metastases from immuno competent but not from -incom petent mice. Thus, the expression of a group of genes involved in prot ein translation and processing was more profoundly altered in endothel ial cells in vivo than in vitro, suggesting that microenviromental fac tors and cell-cell and cell-matrix interactions play an important role . (C) 1998 by The American Society of Hematology.