Involvement of tumor cell integrin alpha v beta 3 in hematogenous metastasis of human melanoma cells

Clin Exp Metastasis. 2002;19(5):427-36. doi: 10.1023/a:1016377114119.


Early metastasis is the primary cause of death in melanoma patients. The adhesion receptor integrin alpha v beta 3 contributes to tumor cell functions that are potentially involved in melanoma growth and metastasis. We tested whether integrin alpha v beta 3 supports metastasis of human melanoma cells when injected into the bloodstream of immune deficient mice. Comparing variants of the same melanoma cell type that expressed either alpha v beta 3, alpha IIb beta 3 or no beta 3 integrin, we found that only alpha v beta 3 strongly supported metastasis. Inhibition of tumor cell alpha v beta 3 function reduced melanoma metastasis significantly and prolonged animal survival. To understand mechanisms that allow alpha v beta 3, but not alpha IIb beta 3 to support melanoma metastasis, we analyzed proteolytic and migratory activities of the melanoma cell variants. Melanoma cells expressing alpha v beta 3, but not those expressing alpha IIb beta 3 or no beta 3 integrin, produced the active form of metalloproteinase MMP-2 and expressed elevated mRNA levels of MT1-MMP and TIMP-2. This indicates an association between alpha v beta 3 expression and protease processing. Furthermore, alpha v beta 3 expression was required for efficient melanoma cell migration toward the matrix proteins fibronectin and vitronectin. The results suggest that expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells and that the related integrin alpha IIb beta 3 cannot substitute for alpha v beta 3 in this respect.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Extracellular Matrix / metabolism
  • Female
  • Fibronectins / metabolism
  • Humans
  • Injections, Intravenous
  • Lung Neoplasms / secondary*
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinases, Membrane-Associated
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Melanoma, Experimental / secondary*
  • Melanoma, Experimental / therapy
  • Metalloendopeptidases / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasm Transplantation
  • Neoplastic Cells, Circulating*
  • Platelet Glycoprotein GPIIb-IIIa Complex / physiology
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Receptors, Vitronectin / immunology
  • Receptors, Vitronectin / physiology*
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tumor Cells, Cultured / transplantation
  • Vitronectin / metabolism


  • Antibodies, Monoclonal
  • Fibronectins
  • Mmp14 protein, mouse
  • Neoplasm Proteins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Vitronectin
  • Vitronectin
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 14