Blood, Vol. 92 No. 9 (November 1), 1998:
pp. 3394-3404
Identification of Four Genes in Endothelial Cells Whose
Expression Is Affected by Tumor Cells and Host Immune Status
A
Study in Ex Vivo-Isolated Endothelial Cells
Birgit Liliensiek,
Marian Rocha,
Victor Umansky,
Axel Benner,
Jie Lin,
Reinhard Ziegler,
Peter P. Nawroth, and
Volker Schirrmacher
From the Department of Internal Medicine I, University of Heidelberg,
Heidelberg; and the German Cancer Research Center, Tumor Immunology
Program and the Division of Biostatistics, Heidelberg, Germany.
A spontaneously metastasizing, well-defined mouse lymphoma was
chosen as an in vivo model to study the effect of tumor-host interaction on gene expression in liver sinusoidal endothelial cells.
Forty-nine bovine aortic endothelial cell (BAEC) genes, recently
isolated by a differential screening approach of a cDNA library
enriched for tumor necrosis factor-
(TNF-) suppressed genes, were
investigated. Four of these genes were finally selected because they were affected differentially by host immuno-competence, TNF-, and tumor cells. Sequence analysis showed them to encode the
bovine polyubiquitin (A4), elongation factor 1 (B2), the acidic
ribosomal phosphoprotein PO (C3), and the ribosomal protein S2 (E10).
Gene expression was analyzed by dot-blot or Northern blot analysis.
TNF- and tumor cell conditioned supernatant suppressed the genes
additive in BAEC but not in other endothelial cells except for bovine
capillary endothelial cells. Ex vivo-isolated liver endothelial cells
of tumor-bearing syngeneic DBA/2 mice showed strong downregulation of
these four genes in comparison to normal control values. In contrast,
endothelial cells of tumor-bearing immuno-incompetent Balb/c (nu/nu)
mice showed no downregulation but upregulation of these genes.
Consistently, all four genes were also downregulated when BAEC were
incubated with supernatants derived from ex vivo-isolated liver
metastases from immuno-competent but not from -incompetent mice. Thus,
the expression of a group of genes involved in protein translation and
processing was more profoundly altered in endothelial cells in vivo
than in vitro, suggesting that microenviromental factors and cell-cell
and cell-matrix interactions play an important role.
© 1998 by The American Society of Hematology.
