Neural-cell adhesion molecule (NCAM) expression by immature and tumor-derived endothelial cells favors cell organization into capillary-like structures.
The neural cell adhesion molecule (NCAM) is widely expressed during embryogenesis, down-regulated in the course of differentiation to be re-expressed during progression of some tumors. We here found that renal tumor-derived endothelial cells (TEC) but not normal endothelial cells (HMEC) expressed NCAM. In TEC, NCAM expression was regulated by the renal embryonic transcription factor PAX2, as transfection with PAX2 antisense abrogated NCAM expression. NCAM stimulation with an agonistic synthetic NCAM peptide enhanced apoptosis resistance and increased ability of TEC to organize in vessel-like structures. The angiogenic effect of NCAM peptide was, at least in part, mediated by the association of NCAM and FGFR1. HMEC transiently acquired NCAM when organized in vessel-like structures after VEGF stimulation or when transfected with PAX2 gene. During the process of VEGF-induced endothelial differentiation of renal stem cells and of circulating endothelial progenitors, NCAM was transiently expressed to disappear at complete endothelial maturation. Targeting NCAM with a saporin-conjugated peptide induced a cytotoxic effect on TEC but not on HMEC. In conclusion, we identified a new role of NCAM in tumor neo-angiogenesis relevant for endothelial cell organization into capillary-like structures. In addition, we found that NCAM expression was associated with an immature phenotype of endothelial cells.
Bussolati
Benedetta
B
Cattedra di Nefrologia, Dipartimento di Medicina Interna and Centro Ricerca Medicina Sperimentale (CeRMS), University of Torino, Ospedale Maggiore S. Giovanni Battista, Corso Dogliotti 14, 10126 Torino, Italy.
Grange
Cristina
C
Bruno
Stefania
S
Buttiglieri
Stefano
S
Deregibus
Maria Chiara
MC
Tei
Lorenzo
L
Aime
Silvio
S
Camussi
Giovanni
G
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009389:Neovascularization, Pathologic / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D043925:Angiogenesis Inducing Agents; D019006:Neural Cell Adhesion Molecules; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A