Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells

Tumor endothelium is critical for solid tumor growth and is a potential site for anticancer drug action. Within 2 h, etoposide caused marked DNA strand breakage in xenograft tumor-derived endothelial cells (TDECs). Etoposide-induced DNA breakage was inhibited by culturing TDECs on gelatin, type IV c...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-09, Vol.56 (18), p.4146-4149
Main Authors: HOYT, D. G, RUSNAK, J. M, MANNIX, R. J, MODZELEWSKI, R. A, JOHNSON, C. S, LAZO, J. S
Format: Article
Language:English
Subjects:
Animals
Antibodies
Antigens, CD - immunology
Antigens, CD - physiology
Antineoplastic agents
Basement Membrane - physiology
Biological and medical sciences
Cell Adhesion
Cell Survival - drug effects
Cells, Cultured
DNA Damage
Endothelium, Vascular - drug effects
Endothelium, Vascular - pathology
Endothelium, Vascular - physiopathology
Etoposide - toxicity
Extracellular Matrix Proteins - physiology
Fibronectins
Fibrosarcoma - blood supply
Gelatin
General aspects
Integrin alpha5
Integrin beta1 - immunology
Integrin beta1 - physiology
Integrin beta3
Integrins - physiology
Laminin
Lipopolysaccharides - toxicity
Medical sciences
Mice
Mice, Inbred C3H
Oligopeptides
Pharmacology. Drug treatments
Platelet Membrane Glycoproteins - immunology
Platelet Membrane Glycoproteins - physiology
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Summary:Tumor endothelium is critical for solid tumor growth and is a potential site for anticancer drug action. Within 2 h, etoposide caused marked DNA strand breakage in xenograft tumor-derived endothelial cells (TDECs). Etoposide-induced DNA breakage was inhibited by culturing TDECs on gelatin, type IV collagen, laminin, fibronectin, and the integrin ligand hexapeptide, GRGDSP, but not the inactive peptide, GRADSP. It was also inhibited when TDECs were on surfaces coated with antibodies to alpha 5, beta 1, or beta 3 integrin subunits and by clustering integrins with soluble antibodies. After 8 h with etoposide, TDECs detached from the monolayer, and 50-kb DNA fragments were seen. Fibronectin inhibited both processes. Thus, integrins are survival factors for TDEC that inhibit the genotoxicity of etoposide and may influence the sensitivity of tumors to drugs.
ISSN:0008-5472
1538-7445