Elena Ostroumov1, Christopher J Hunter. 1. From the Centre for Bioengineering Research and Education, University of Calgary, Calgary, Alberta, Canada.
Abstract
STUDY DESIGN: 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. 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 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. CONCLUSION: 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.
STUDY DESIGN: 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. 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 and HGF expression, localization, and function in humanchordoma 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. CONCLUSION: 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 chordomapatients, our results are a valuable and promising addition to the current situation in managing chordomas.
Authors: Beatriz A Walter; Maria Begnami; Vladimir A Valera; Mariarita Santi; Elisabeth J Rushing; Martha Quezado Journal: J Neurooncol Date: 2010-07-10 Impact factor: 4.130
Authors: Jason M Davies; Aaron E Robinson; Cynthia Cowdrey; Praveen V Mummaneni; Gregory S Ducker; Kevan M Shokat; Andrew Bollen; Byron Hann; Joanna J Phillips Journal: J Neurosurg Date: 2013-11-29 Impact factor: 5.115