A human sacral chordoma
cell line, CCL3, was established and in vitro
characterization of c-Met
oncoprotein in chordoma
cells was performed.
Determination of whether c-Met
plays an important role in chordoma
Summary of Background Data.
Chordomas are malignant life-threatening tumors that arise from the remnants of the notochord. c-Met
is an oncoprotein that is expressed by a variety of solid tumors, including chordomas, and HGF
is its high affinity ligand. In the present study, we investigated c-Met
expression, localization, and function in human chordoma
SDS-PAGE, Western blotting
techniques, and cell migration
functional assays were used to asses c-Met
expression, localization, and functional activity.
Intracellular protein tyrosine phosphorylation
was enhanced on HGF
binding, and an increase in the amount of 50 kDa α-chain of c-Met
was detected in HGF
-stimulated cells. Immunostaining of c-Met
revealed membrane/cytoplasmic localization in nonstimulated cells, and perinuclear colocalization
-stimulated cells. Positive chemotactic and migration
activity in response to HGF
was also demonstrated.
Our data supports our hypothesis that the c-Met
oncoprotein plays a leading role in the metastatic process in chordomas, and that a c-Met
pair is involved in chordoma
malignancy. Taking into consideration the very limited treatment options and an extremely poor prognosis for the chordoma
patients, our results are a valuable and promising addition to the current situation in managing chordomas.