title: Breast tumor cells transendothelial migration induces endothelial cell anoikis through extracellular matrix degradation.
abstract: Mutual interactions between human breast cancer cells and endothelial cells were studied in a model mimicking tumor cell intravasation. MDA-MB-231 tumor cells and human umbilical vein endothelial cells (HUVEC) were cocultured on opposite sides of a Transwell filter allowing tumor cell contacts with the basement membrane of the HUVEC forming endothelium and tumor cell transendothelial migration. Confocal microscopy analysis showed that transmigrating MDA-MB-231 cells lay under the HUVEC, thereby inducing HUVEC detachment and tumor cell-HUVEC contact-dependent apoptosis. GM6001 a matrix metalloproteinase (MMP) inhibitor inhibited almost completely, the MDA-MB-231 cell transendothelial migration and the anoikis process. In this intravasation model, a tumor cell invasive mechanism was demonstrated (i) induction of extensive endothelial anoikis induced by degradation of the extracellular matrix (ECM) components, (ii) activation of pro-matrix metalloproteinase (MMP)-2 into MMP-2 by the MT1-MMP-TIMP (tissue inhibitor metalloproteinase) 2-pro-MMP-2 membrane complex and (iii) attraction and migration of metastatic cell through apoptotic endothelium. These interactions could partly explain the necrosis-angiogenesis relationship in tumor angiogenesis.
authors.affiliation: INSERM Unité 553, Hôpital Saint-Louis, F 75475 Paris cedex 10, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Peyri
authors.forename: Madeleine
authors.initials: M
authors.lastname: Berard
authors.forename: Françoise
authors.initials: F
authors.lastname: Fauvel-Lafeve
authors.forename: Veronique
authors.initials: V
authors.lastname: Trochon
authors.forename: Brigitte
authors.initials: B
authors.lastname: Arbeille
authors.forename: He
authors.initials: H
authors.lastname: Lu
authors.forename: Chantal
authors.initials: C
authors.lastname: Legrand
authors.forename: Michel
authors.initials: M
authors.lastname: Crepin
mesh_terms: D023102:Anoikis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D020782:Matrix Metalloproteinases; D053511:Matrix Metalloproteinase 14