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Hepatocyte growth factor decreases sensitivity to chemotherapeutic agents and stimulates cell adhesion, invasion, and
1Laboratory of Molecular Oncology, Albert Einstein College of Medicine, New Hyde Park, New York, 11040, USA.
Abstract:
Hepatocyte growth factor (HGF), also known as scatter factor (SF), plays an important role in cell:cell adhesion, cell proliferation, motility, and invasiveness of epithelial cells and tumor cells. In this study, we examined the effects of HGF on these types of biological activities and chemosensitivity in Chinese hamster ovary (CHO) cells by stable transfection of the HGF gene. HGF-transfected clones produced very high titers of HGF protein, whereas control vector-transfected clones did not produce detectable HGF protein. HGF-transfected clones showed modestly increased proliferation rates and became more resistant to cell death and apoptosis caused by two anticancer drugs, adriamycin (ADR) and camptothecin (CPT), compared to controlvector-transfected clones. Furthermore, HGF-transfected clones also exhibited increased activities of cell adhesion, migration, and invasion. The current study is the first demonstration that overexpression of the HGF gene affects chemosensitivity and cell metastasis behaviors, suggesting that HGF signaling pathway is a promising new target of therapeutic intervention of tumors.
Insights
Hepatocyte growth factor (HGF) gene overexpression in CHO cells increased cell proliferation, migration, and invasion. HGF also enhanced resistance to anticancer drugs, suggesting HGF signaling as a therapeutic target for tumors.
Area of Science:
- Cell Biology
- Molecular Biology
- Oncology
Background:
- Hepatocyte growth factor (HGF), also known as scatter factor (SF), is crucial for epithelial and tumor cell functions, including adhesion, proliferation, motility, and invasion.
- Understanding HGF's role in cellular behavior and drug response is vital for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the impact of HGF gene overexpression on biological activities and chemosensitivity in Chinese hamster ovary (CHO) cells.
- To explore the potential of the HGF signaling pathway as a therapeutic target for tumors.
Main Methods:
- Stable transfection of the HGF gene into CHO cells.
- Comparison of HGF-producing clones with control vector-transfected clones.
- Assessment of cell proliferation, apoptosis, chemosensitivity (to adriamycin and camptothecin), adhesion, migration, and invasion.
Main Results:
- HGF-transfected clones produced high levels of HGF protein.
- Modestly increased proliferation rates were observed in HGF-transfected clones.
- HGF-transfected clones exhibited enhanced resistance to adriamycin (ADR) and camptothecin (CPT)-induced cell death and apoptosis.
- Increased activities of cell adhesion, migration, and invasion were noted in HGF-transfected clones.
Conclusions:
- HGF gene overexpression significantly affects chemosensitivity and cell metastasis-related behaviors.
- The HGF signaling pathway represents a promising new target for tumor therapeutic intervention.