C-met activation is necessary but not sufficient for liver colonization by B16 murine melanoma cells

Clin Exp Metastasis. 1998 Apr;16(3):253-65. doi: 10.1023/a:1006596909948.


Metastasis to the liver is a frequent event in clinical oncology, the molecular mechanisms of which are not fully understood. We have recently reported a consistent overexpression of c-met in B16 melanoma cells selected in vivo for enhanced liver metastatic ability. In this study we address the question as to whether constitutive activation of c-met is a necessary and sufficient condition for enhanced liver colonization by B16 melanoma cells. Different levels of c-met expression and/or activation in B16 cells were achieved by subcloning, or by c-DNA transfection with either HGF/SF or the oncogenic form of c-met (tpr-met). Metastatic ability of the different populations was then evaluated in vivo by the lung colonization (experimental metastasis) assay. Results indicate that c-met (but not tpr-met) activation in B16 melanoma cells may increase their liver colonizing potential, probably by enhancing motility and invasion in response to paracrine interactions with its ligand. C-met expression per se, however, is not able to change the organ specificity of the cells. C-met activation appears instead to be required at later stages of liver colonization by B16 melanoma cells, in order to enhance their site-specific metastatic ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autocrine Communication
  • Enzyme Activation
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Liver Neoplasms / secondary*
  • Lung Neoplasms / secondary
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Mice
  • Neoplasm Metastasis*
  • Phosphotyrosine / metabolism
  • Proto-Oncogene Proteins c-met / metabolism*
  • Tumor Cells, Cultured


  • Phosphotyrosine
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met