Transforming growth factor-beta 1 increases the adhesion of MDA-MB-231 mammary adenocarcinoma cells to the microvascular subendothelium.
The increase of tumor cell adhesion to the subendothelium in the presence of TGF-beta 1 is thought to be mediated by two major events: an enrichment of extracellular matrix proteins secreted by endothelial cells and an increase of the integrins on the surface of tumor cells. In this study, we analyzed the effect of TGF-beta 1 on the adhesion of a mammary adenocarcinoma cell line (MDA-MB-231) to the matrix of human microvascular endothelial cells (HMEC-1). The adhesion of TGF-beta 1-treated tumor cells to a non-treated matrix or to purified matrix proteins was enhanced, while no increase was observed when non-treated tumor cells were let to adhere to a matrix secreted by HMEC-1 in the presence of the cytokine. Thus, the increase of cell adhesion was due to the effect of TGF-beta 1 on tumor cells and not to the matrix enrichment induced by this cytokine. The hyper-adhesion was inhibited by the RGD peptide and EDTA indicating that integrins were involved. Integrin subunits concentrations (alpha 5, alpha v and beta 1) on the surface of TGF-beta 1-treated tumor cells were not modified, while confocal microscopy showed a reorganization of beta 1 integrin subunits on the cell surface and in the cytoplasm resulting in actin fibers reorganization in the cytoskeleton. This indicates that the enhanced adhesion of TGF-beta 1-treated MDA-MB-231 cells to the subendothelium is due to a qualitative change of integrins.
Loganadane
L D
LD
Unité 353 INSERM "Protéines Adhésives et Protéases des Cellules Vasculaires et Sanguines", Paris, France.
Vassy
J
J
Legrand
C
C
Fauvel-Lafeve
F
F
D000818:Animals; D051242:Caveolin 1; D022461:Caveolins; D002448:Cell Adhesion / Q000502:physiology*; D004492:Edetic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000187:drug effects / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D051242:Caveolin 1; D022461:Caveolins; D016023:Integrins; D008565:Membrane Proteins; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid; D006493:Heparin; D004492:Edetic Acid