Abstract:
:Rapid growth of residual tumor after partial hepatectomy has been observed during the period of liver regeneration in children with malignant embryonal hepatoblastoma. The aim of this study was to elucidate the role of hepatocyte growth-factor-scatter factor (HGF-SF) in this phenomenon. Markedly increased serum levels of HGF-SF up to 15 ng/ml were found in 13/18 patients after liver resection and in 6/16 patients with regressive tumors after chemotherapy, in comparison with 15 patients with non-pre-treated hepatoblastoma and 20 healthy children of the same age group. In the tumors, epithelial tumor cells highly expressed the HGF-SF receptor c-met, as shown by immunohistochemistry and m-RNA RT-PCR. The hepatoblastoma cell lines HepT1, HepT3 and HUH6 reacted with significantly increased proliferation to rhHGF-SF in these concentrations (1-15 ng/ml). In the tumors, HGF-SF was found to be expressed in the stromal fibroblasts. In culture, hepatoblastoma cells (HepT3, HUH6) stimulated secretion of the factor by human fibroblasts, indicating the paracrine fashion of intratumoral HGF-SF production. Cultured hepatoblastoma cells ceased to proliferate at 20-50 ng/ml HGF-SF, and they underwent cell death at >/=100 ng/ml. In contrast, the hepatocellular-carcinoma cell line HepG2 decreased growth under HGF-SF in a dose-dependent manner. We conclude that post-operatively secreted and intratumorally produced HGF-SF can function as a growth factor for hepatoblastoma, while the same agent has a cytostatic effect in unphysiologically high concentrations.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
von Schweinitz D,Faundez A,Teichmann B,Birnbaum T,Koch A,Hecker H,Glüer S,Fuchs J,Pietsch Tdoi
10.1002/(SICI)1097-0215(20000115)85:2<151::AID-IJCkeywords:
subject
Has Abstractpub_date
2000-01-15 00:00:00pages
151-9issue
2eissn
0020-7136issn
1097-0215pii
10.1002/(SICI)1097-0215(20000115)85:2<151::AID-IJCjournal_volume
85pub_type
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