title: Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells.
abstract: The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.
authors: Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratório de Biologia da Célula Endotelial e da Angiogênese (LabAngio),Universidade do Estado do Rio de Janeiro, Rua São Francisco Xavier, Rio de Janeiro, Brazil.
authors: Tercia Rodrigues
authors: TR
authors: Alves
authors: Anna Carolina Carvalho
authors: AC
authors: da Fonseca
authors: Sara Santana
authors: SS
authors: Nunes
authors: Aline Oliveira
authors: AO
authors: da Silva
authors: Luiz Gustavo Feijó
authors: LG
authors: Dubois
authors: Jane
authors: J
authors: Faria
authors: Suzana Assad
authors: SA
authors: Kahn
authors: Nathan Bessa
authors: NB
authors: Viana
authors: Jorge
authors: J
authors: Marcondes
authors: Chantal
authors: C
authors: Legrand
authors: Vivaldo
authors: V
authors: Moura-Neto
authors: Verônica
authors: V
authors: Morandi
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D019063:Tenascin / Q000378:metabolism*
chemical_list: D019063:Tenascin