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Updated: Aug 26, 2026
Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
Published on: September 10, 2014
Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin
Andrea Rasola1, Sergio Anguissola, Norma Ferrero
1Division of Molecular Oncology, Institute for Cancer Research and Treatment, University of Torino Medical School, Candiolo, Italy. andrea.rasola@ircc.it
Abstract:
The hepatocyte growth factor (HGF) receptor, encoded by the MET oncogene, is expressed in approximately 70% of human ovarian carcinomas and overexpressed in 30% of cases. Because HGF is known to protect cells from apoptosis, we investigated whether receptor expression modifies ovarian cancer cell response to chemotherapy. The apoptotic effect of the front-line chemotherapeutic drugs paclitaxel and cisplatin on cells treated with HGF was studied. In ovarian cancer cell lines, pretreatment with HGF surprisingly enhances the apoptotic response to low doses of paclitaxel and cisplatin. HGF empowers specifically the intrinsic apoptotic pathway, whereas it protects cells from extrinsic Fas-induced apoptosis. Chemotherapy sensitization is specific for HGF because another growth factor (e.g., epidermal growth factor) increases ovarian cancer cell survival. In nonovarian cancer cell models, as expected, HGF provides protection from drug-induced apoptosis. These data show that HGF sensitizes ovarian carcinoma cells to low-dose chemotherapeutic agents. This suggests that HGF may be used to improve response to chemotherapy in a set of human ovarian carcinomas molecularly classified based on the MET oncogene expression.
Insights
Hepatocyte growth factor (HGF) surprisingly enhances ovarian cancer cell apoptosis when treated with low-dose chemotherapy. This finding suggests HGF may improve treatment response in MET-expressing ovarian carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- The MET oncogene encodes the hepatocyte growth factor (HGF) receptor, implicated in various cancers.
- HGF receptor expression is prevalent in human ovarian carcinomas, with overexpression in a significant subset.
- HGF is generally known for its cytoprotective effects, including resistance to apoptosis.
Purpose of the Study:
- To investigate if HGF receptor expression influences ovarian cancer cell sensitivity to chemotherapy.
- To determine the effect of HGF on the apoptotic response of ovarian cancer cells to paclitaxel and cisplatin.
- To elucidate the specific apoptotic pathways modulated by HGF in ovarian cancer.
Main Methods:
- Utilized ovarian cancer cell lines for in vitro studies.
- Pretreated cells with HGF before administering front-line chemotherapeutic agents (paclitaxel and cisplatin).
- Analyzed the apoptotic response, differentiating between intrinsic and extrinsic pathways (Fas-induced apoptosis).
Main Results:
- HGF pretreatment unexpectedly enhanced apoptosis in ovarian cancer cells exposed to low-dose paclitaxel and cisplatin.
- HGF specifically bolstered the intrinsic apoptotic pathway.
- HGF demonstrated a protective effect against extrinsic Fas-induced apoptosis.
- Chemotherapy sensitization was specific to HGF; epidermal growth factor promoted cell survival.
- In non-ovarian cancer models, HGF exhibited its expected protective role against drug-induced apoptosis.
Conclusions:
- Hepatocyte growth factor (HGF) sensitizes ovarian carcinoma cells to low-dose chemotherapeutic agents.
- This sensitization is linked to the modulation of the intrinsic apoptotic pathway.
- These findings suggest a potential therapeutic strategy using HGF to improve chemotherapy response in ovarian carcinomas characterized by MET oncogene expression.
