Endothelial cell apoptosis is inhibited by a soluble factor secreted by human colon cancer cells.
In contrast to normal tissues, tumors are exposed to adverse environmental conditions, such as hypoxia and acidity. Despite this caustic environment, tumor cells and supporting vascular structures survive the latter, providing nutrients and oxygen to facilitate tumor growth. Therefore, we hypothesized that cancer cells express factors that protect endothelial cells from apoptosis. Human umbilical vein endothelial cells were grown in serum-free medium or in medium conditioned by either human colon cancer cells or non-malignant cells. Endothelial cells grown in medium conditioned by colon cancer cells demonstrated a decrease in apoptosis, whereas endothelial cells grown in medium conditioned by non-malignant cells did not. Erk-1/2 phosphorylation increased when endothelial cells were incubated in medium conditioned by colon cancer cells but not when cells were incubated in medium conditioned by non-malignant cells. Protein fractions from medium conditioned by colon cancer cells that were < 3 kDa protected endothelial cells from apoptosis and activated Erk-1/2. Heat-inactivated conditioned media did not protect endothelial cells from apoptosis and did not activate Erk-1/2. Human colon cancer cells secrete a soluble factor or factors that inhibit endothelial cell apoptosis. This factor is likely to be a protein or protein fragment because it loses its activity after heat inactivation. These studies support the hypothesis that tumor cells can alter the phenotype of endothelial cells.
Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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Davis
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Ramirez
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McConkey
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Ellis
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005591:Chemical Fractionation; D003110:Colonic Neoplasms / Q000378:metabolism*; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology*; D004789:Enzyme Activation; D006133:Growth Substances / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D008222:Lymphokines / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases