C-met activation is necessary but not sufficient for liver colonization by B16 murine melanoma cells.
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.
Lin
S
S
Friedrich Miescher Institut, Basel, Switzerland.
Rusciano
D
D
Lorenzoni
P
P
Hartmann
G
G
Birchmeier
W
W
Giordano
S
S
Comoglio
P
P
Burger
M M
MM
D000818:Animals; D019898:Autocrine Communication; D004789:Enzyme Activation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D019000:Phosphotyrosine / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D019000:Phosphotyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met