Vitronectin expression in differentiating neuroblastic tumors: integrin alpha v beta 5 mediates vitronectin-dependent adhesion of retinoic-acid-differentiated neuroblastoma cells

Am J Pathol. 1997 May;150(5):1631-46.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / pathology
  • Cell Adhesion
  • Cell Differentiation / drug effects
  • Ganglia, Sensory / metabolism
  • Ganglia, Sensory / pathology
  • Ganglioneuroma / metabolism
  • Ganglioneuroma / pathology
  • Humans
  • Integrins / physiology*
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology*
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / pathology
  • RNA, Messenger / biosynthesis
  • Receptors, Vitronectin / biosynthesis
  • Schwann Cells / metabolism
  • Schwann Cells / pathology
  • Tretinoin / physiology*
  • Vitronectin / biosynthesis*
  • Vitronectin / genetics

Substances

  • Integrins
  • RNA, Messenger
  • Receptors, Vitronectin
  • Vitronectin
  • integrin alphaVbeta5
  • Tretinoin