Vitronectin expression in differentiating neuroblastic tumors: integrin alpha v beta 5 mediates vitronectin-dependent adhesion of retinoic-acid-differentiated neuroblastoma cells.
The metastatic potential of undifferentiated neuroblastomas is typically lost when differentiation into ganglioneuroblastomas occurs spontaneously or is induced. Cell adhesion may play a role in metastasis, and we have shown recently that expression of integrin alpha v beta 5 protein and mRNA is up-regulated in ganglioneuroblastomas in vivo. To investigate whether interactions of alpha v beta 5 with matrix components play a role in the loss of metastatic potential, we used immunohistochemical and in situ hybridization to analyze neuroblastic tumors at various stages of differentiation for expression of the alpha v beta 5 ligands, vitronectin and osteopontin, and determined the ability of vitronectin to promote attachment and neurite outgrowth in vitro in a retinoic-acid-differentiated neuroblastoma cell model. We found that vitronectin, but not osteopontin, was expressed in 5 of 5 ganglioneuroblastomas but was absent or weakly expressed in 6 of 6 undifferentiated neuroblastomas. Neuronal cell vitronectin was detected in 7 of 9 ganglioneuromas, 5 of 8 peripheral ganglia, and 14 of 21 adrenal gland medullae, confirming expression of vitronectin in mature peripheral neurons. In vitro, vitronectin promoted attachment of both undifferentiated and retinoic-acid-differentiated neuroblastoma cells, which was inhibited 20 and 60%, respectively, by monoclonal antibody anti-integrin alpha v beta 5. Vitronectin-promoted neurite outgrowth of retinoic-acid-differentiated neuroblastoma cells was not inhibited by monoclonal antibody anti-alpha v beta 5. These data suggest that the synthesis of vitronectin and the ability of integrin alpha v beta 5 to mediate vitronectin adhesion on retinoic-acid-differentiated neuroblastoma cells may promote differentiation of neuroblastoma cells in vivo.
Gladson
C L
CL
Department of Pathology, University of Alabama at Birmingham 35294, USA.
Dennis
C
C
Rotolo
T C
TC
Kelly
D R
DR
Grammer
J R
JR
D000310:Adrenal Gland Neoplasms / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000187:drug effects; D017950:Ganglia, Sensory / Q000378:metabolism / Q000473:pathology; D005729:Ganglioneuroma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D019030:Receptors, Vitronectin / Q000096:biosynthesis; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000502:physiology*; D019096:Vitronectin / Q000096:biosynthesis* / Q000235:genetics
D016023:Integrins; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D014212:Tretinoin