Isolation and characterization of human breast tumor-derived endothelial cells.
Increasing evidence indicates that tumor-derived endothelial cells (TEC) possess a distinct and unique phenotype in respect to normal endothelial cells and may be able to acquire resistance to drugs. However, few functional studies are available on cultured TEC. In the present study, we obtained TEC from human breast carcinomas and, to dispel the possibility of contaminating tumor cells, we established six different clones that we characterized at a functional level. Breast TEC cell lines and clones did not undergo normal cell senescence in culture and showed constant expression of markers of endothelial activation and angiogenesis. These cells showed increased apoptosis resistance to vincristine and doxorubicin and increased random cell motility, as compared to normal micro-endothelial cells. In addition, breast TEC, at variance to normal endothelial cells, were able to grow and to organize in the absence of serum in capillary-like structures on Matrigel that persisted up to one week. These functional characteristics of breast TEC may be relevant for tumor angiogenesis and may indicate an increased pro-angiogenic activity of endothelial cells within the tumor. Moreover, our data suggest that TEC might be more appropriate for screening antiangiogenic drugs than normal endothelial cells.
Grange
Cristina
C
Department of Internal Medicine, University of Torino, Corso Dogliotti 14, 10126 Torino, Italy.
Bussolati
Benedetta
B
Bruno
Stefania
S
Fonsato
Valentina
V
Sapino
Anna
A
Camussi
Giovanni
G
D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001943:Breast Neoplasms / Q000098:blood supply*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic; D014750:Vincristine / Q000494:pharmacology
D015703:Antigens, CD; D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin