Specific alpha v integrin receptors modulate K1735 murine melanoma cell behavior

Biochem Biophys Res Commun. 2003 Sep 5;308(4):814-9. doi: 10.1016/s0006-291x(03)01477-3.

Abstract

Expression of beta 3 integrins is increased in invasive melanoma. In this study we show that K1735 cell proliferation is enhanced by the expression of either beta 3 or a constitutively active Src. We investigated possible modulators of FN matrix assembly and found that matrix metalloproteinase 2 (MMP2) was activated by alpha v beta 3. alpha v beta 3 integrin was localized to focal contacts whereas alpha v beta 5 was peripherally distributed. MMP2 was also activated by expression of CASrc. MMP2 activation inversely correlated with FN matrix assembly, in that it dramatically reduced the organization of a FN matrix. K1735 cell migration on VN and invasion through a reconstituted basement membrane were decreased in the presence of anti-MMP2 antibodies. These results demonstrate that the expression of the alpha v beta 3 complex modulates melanoma cell behavior including activation of Src, organization of the cytoskeleton, assembly of the extracellular matrix, cell motility, and activation of MMP2.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Bromodeoxyuridine / pharmacology
  • Cell Division
  • Cell Movement
  • Coloring Agents / pharmacology
  • Cricetinae
  • Cytoskeleton / metabolism
  • Enzyme Activation
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism
  • Integrin alphaV / metabolism
  • Integrin alphaV / physiology*
  • Integrin alphaVbeta3 / metabolism*
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Neoplasm Invasiveness
  • Phenotype
  • Retroviridae / genetics
  • Tetrazolium Salts / pharmacology
  • Thiazoles / pharmacology
  • Tumor Cells, Cultured
  • Vitronectin / metabolism
  • src-Family Kinases / metabolism

Substances

  • Coloring Agents
  • Fibronectins
  • Integrin alphaV
  • Integrin alphaVbeta3
  • Tetrazolium Salts
  • Thiazoles
  • Vitronectin
  • src-Family Kinases
  • Matrix Metalloproteinase 2
  • thiazolyl blue
  • Bromodeoxyuridine