Magic Roundabout, a Tumor Endothelial Marker: Expression and Signaling

Biochem Biophys Res Commun. 2005 Jul 1;332(2):533-41. doi: 10.1016/j.bbrc.2005.03.250.

Abstract

Molecular signals that guide blood vessels to specific paths are not fully deciphered, but are thought to be similar to signals that mediate neuronal guidance. These cues are not only critical for normal blood vessel development, but may also play a major role in tumor angiogenesis. In this study, we have demonstrated the tumor endothelial specific expression of a Robo family member, magic roundabout (MRB), functionally characterized its role in endothelial cell migration and defined a signaling pathway that might mediate this function. We show that MRB is differentially over-expressed in tumor endothelial cells versus normal adult endothelial cells in numerous solid tumors. Moreover, over-expression of MRB in endothelial cells activates MRB in a ligand-independent fashion, and activation of MRB via Slit2, a putative ligand, results in inhibition of VEGF and FGF induced migration. We also demonstrate that MRB induced inhibition of endothelial migration is partially mediated by the Ras-Raf-Mek-Erk signaling pathway. We therefore hypothesize that expression of MRB is involved in regulating the migration of endothelial cells during tumor angiogenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Neoplasms / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction*
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • ROBO4 protein, human
  • Receptors, Cell Surface
  • Slit homolog 2 protein