Overexpression of the hepatocyte growth factor (HGF) receptor (Met) and presence of a truncated and activated intracellular HGF receptor fragment in locally aggressive/malignant human musculoskeletal tumors
V. Wallenius et al., Overexpression of the hepatocyte growth factor (HGF) receptor (Met) and presence of a truncated and activated intracellular HGF receptor fragment in locally aggressive/malignant human musculoskeletal tumors, AM J PATH, 156(3), 2000, pp. 821-829
Citations number
39
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Enhanced hepatocyte growth factor (HGF) receptor (Met) signaling has been s
uggested to play an important role in the development and progression of va
rious epithelial and nonepithelial tumors. N-terminally truncated forms of
the HGF receptor have been shown to be constitutively activated and tumorig
enic in animal experiments. In the present study, 102 benign and malignant
human musculoskeletal tumors were examined for expression of the HGF recept
or by Western blotting and/or immunohistochemistry. A clear predominance of
HGF receptor expression was seen in malignant as compared to benign tumors
(Western blotting, P < 0.001; immunohistochemistry, P < 0.02). For the fir
st time we show HGF receptor expression in the following four tumor types:
dermatofibrosarcoma protuberans, clear cell sarcoma of tendons, malignant p
rimitive neuroectodermal tumor, and benign fibrous histiocytoma, In three c
ases of sarcoma with high HGF receptor expression by Western blotting, we f
ound indications of a short 85-kd N-terminally truncated HGF receptor that
was tyrosine phosphorylated and located in the cytoplasm, Although fragment
s of this length were seen in 18 of 65 tumors, most were not tyrosine-phosp
horylated. Northern blotting revealed only the 7.5-kb full-length HGF recep
tor transcript, suggesting that the 85-kd fragment is generated by an alter
native initiation of translation or by proteolytic cleavage. Southern blott
ing detected no amplification of the Hgfr/Met gene in the 35 tumors examine
d, in contrast to our recent report of Hgfr/Met gene amplification in 7,12-
dimethylbenz(a)anthracene (DMBA)-induced rat sarcomas, The present data sug
gest that the locally aggressive and malignant properties of human mesenchy
mal tumors maybe related, in part, to high levels of full-length HGF recept
ors, and in some cases to the occurrence of N-terminally truncated HGF rece
ptors, activated independently of HGF.