Identifying mechanisms for therapeutic intervention in chordoma: c-Met oncoprotein.
METHODS
A human sacral chordoma cell line, CCL3, was established and in vitro characterization of c-Met oncoprotein in chordoma cells was performed.


OBJECTIVE
Determination of whether c-Met plays an important role in chordoma's malignancy.


BACKGROUND
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 and HGF expression, localization, and function in human chordoma cells.


METHODS
SDS-PAGE, Western blotting, immunofluorescence techniques, and cell migration functional assays were used to asses c-Met and HGF expression, localization, and functional activity.


RESULTS
Intracellular protein tyrosine phosphorylation was enhanced on HGF binding, and an increase in the amount of 50 kDa alpha-chain of c-Met was detected in HGF-stimulated cells. Immunostaining of c-Met and HGF revealed membrane/cytoplasmic localization in nonstimulated cells, and perinuclear colocalization in HGF-stimulated cells. Positive chemotactic and migration activity in response to HGF was also demonstrated.


CONCLUSIONS
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-HGF 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.
Ostroumov
Elena
E
From the Centre for Bioengineering Research and Education, University of Calgary, Calgary, Alberta, Canada.
Hunter
Christopher J
CJ
D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002817:Chordoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005260:Female; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000378:metabolism*; D013125:Spinal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*
D014408:Biomarkers, Tumor; C066855:HGF protein, human; D021122:Protein Subunits; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met