ESTABLISHMENT OF A FUNCTIONAL HGF C-MET AUTOCRINE LOOP IN SPONTANEOUSTRANSFORMANTS OF WB-F344 RAT-LIVER STEM-LIKE CELLS/

Citation
Sc. Presnell et al., ESTABLISHMENT OF A FUNCTIONAL HGF C-MET AUTOCRINE LOOP IN SPONTANEOUSTRANSFORMANTS OF WB-F344 RAT-LIVER STEM-LIKE CELLS/, Hepatology, 28(5), 1998, pp. 1253-1259
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenterology & Hepatology
Journal title
ISSN journal
0270-9139
Volume
28
Issue
5
Year of publication
1998
Pages
1253 - 1259
Database
ISI
SICI code
0270-9139(1998)28:5<1253:EOAFHC>2.0.ZU;2-Q
Abstract
A model of spontaneous malignant transformation was used to evaluate t he molecular changes that take place in WB-F344 rat liver epithelial c ells during neoplastic transformation and tumorigenesis, A comparison of wild-type low-passage WB-F344 cells to spontaneously transformed tu mor cell lines revealed that the majority of the tumor cell lines have an increased capacity for autonomous proliferation and motility when maintained in serum-free media. In the current study, we show that c-m ct is expressed at some level in wild-type WB-F344 cells and in all of the spontaneously transformed tumor cell lines, and that 9/16 of the tumor cell lines have acquired hepatocyte growth factor (HGE) expressi on. In vitro growth of HGF-expressing tumor cell lines is inhibited as much as 68% by the addition of neutralizing antibodies to HGF or anti sense HGF oligonucleotides, indicating that the production of HGF by t he tumor cells is partially responsible for driving autonomous prolife ration in a subset of tumor cell lines. Furthermore, conditioned media collected from HGF-expressing tumor cell lines stimulates DNA synthes is in wild-type WB-F344 cells, and this effect can be abrogated by pre -incubation of the conditioned media with neutralizing antibodies to H GE Because HGF is a motility-promoting growth factor, all cell lines w ere evaluated to determine if expression of HGF stimulated motogenesis , All turner cell lines (regardless of HGF expression) were highly mot ile in comparison with wild-type WB-F344 cells, with a 3.5-fold to 20- fold greater number of motile cells. The high basal rate of motility c haracteristic of the tumor cell lines is not a result of the productio n of HGF, because it is also a property of the cell Lines that do not express HGF messenger RNA. Furthermore, tumor cell motility is not inh ibited by antisense oligonucleotides or neutralizing antibodies. Estab lishment of an autocrine HGF/c-met loop in a subset of spontaneously t ransformed WB-F344 cell lines may influence development and/or express ion of the tumorigenic phenotype by driving cellular proliferation.