TY - JOUR
T1 - Retrogenic expression of the MET proto-oncogene correlates with the invasive phenotype of human rhabdomyosarcomas
AU - Ferracini, Riccardo
AU - Olivero, Martina
AU - Di Renzo, Maria Flavia
AU - Martano, Marina
AU - De Giovanni, Carla
AU - Nanni, Patrizia
AU - Basso, Giuseppe
AU - Scotlandi, Katia
AU - Lollini, Pier Luigi
AU - Comoglio, Paolo M.
PY - 1996
Y1 - 1996
N2 - The MET oncogene encodes the receptor for HGF/ Scatter Factor, known to control cell motility and invasion in epithelial cells. We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhabdomyosarcomas. In both the embryonal and alveolar histotypes the oncogene is overexpressed and, in some cases, amplified. The Met receptor is exposed at the cell surface and is functionally active in response to HGF/Scatter Factor. Accordingly, rhabdomyosarcoma cells exhibit an invasive phenotype in vitro in response to exogenous HGF/Scatter factor. As the factor is known to be produced by connective tissues, a paracrine stimulation of rhabdomyosarcoma invasiveness in vivo is hypothesized. Two alveolar rhabdomyosarcomas were found to co-express the 'two-kringle' alternatively-spliced HGF/Scatter Factor variant, which has been previously shown to stimulate cell motility and matrix invasion in vitro. These cells displayed the invasive phenotype in the absence of exogenous HGF/Scatter Factor, suggesting an autocrine mechanism in vivo. These data indicate that aberrant expression of the provides rhabdomyosarcoma cells with the same property as embryonal myoblasts to migrate into the surrounding connective tissues.
AB - The MET oncogene encodes the receptor for HGF/ Scatter Factor, known to control cell motility and invasion in epithelial cells. We report that the Met/HGF receptor, absent in differentiated adult skeletal muscles, is aberrantly expressed in clinical samples and in established cell lines of human rhabdomyosarcomas. In both the embryonal and alveolar histotypes the oncogene is overexpressed and, in some cases, amplified. The Met receptor is exposed at the cell surface and is functionally active in response to HGF/Scatter Factor. Accordingly, rhabdomyosarcoma cells exhibit an invasive phenotype in vitro in response to exogenous HGF/Scatter factor. As the factor is known to be produced by connective tissues, a paracrine stimulation of rhabdomyosarcoma invasiveness in vivo is hypothesized. Two alveolar rhabdomyosarcomas were found to co-express the 'two-kringle' alternatively-spliced HGF/Scatter Factor variant, which has been previously shown to stimulate cell motility and matrix invasion in vitro. These cells displayed the invasive phenotype in the absence of exogenous HGF/Scatter Factor, suggesting an autocrine mechanism in vivo. These data indicate that aberrant expression of the provides rhabdomyosarcoma cells with the same property as embryonal myoblasts to migrate into the surrounding connective tissues.
KW - Hepatocyte growth factor
KW - Proto-oncogenes
KW - Rhabdomyosarcoma
KW - Tyrosine kinase receptors
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M3 - Article
C2 - 8622890
AN - SCOPUS:0011701480
VL - 12
SP - 1697
EP - 1705
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 8
ER -