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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
Changes in epidermal growth factor receptor expression in human bladder cancer cell lines following interferon-alpha
Xian-Jun Qu1, Jia-Lin Yang, Pamela J Russell
1Department of Pharmacology, College of Pharmacy, Shandong University, Jinan, People's Republic of China.
Purpose:
We examined the regulation of epidermal growth factor (EGF) receptor (EGFR) expression in human bladder cancer cell lines by interferon-alpha (IFN-alpha), the ability of IFN-alpha to inhibit cell proliferation and the sensitivity of IFN-alpha pretreated cells to EGF.
Materials And Methods:
Cell proliferation was determined using crystal violet colorimetric and clonogenic assays. EGFR expression was measured by flow cytometry using specific antibody or ligand binding approaches.
Results:
After IFN-alpha (100 IU/ml) treatment cell surface EGFR expression was upregulated in 6 of 11 and down-regulated in 2 of 11 bladder cancer cell lines. The over expression of cell surface EGFR peaked within 48 to 96 hours and increased by 35% to 241% in individual cell lines. High level cell surface EGFR correlated with intracellular EGFR expression. Cell growth inhibition by IFN-alpha coexisted with EGFR over expression in the 6 lines. IFN-alpha treated cells remained sensitive to EGF treatment.
Conclusions:
IFN-alpha transiently up-regulates EGFR expression and inhibits in vitro growth in some human bladder cancer cells. IFN-alpha does not prevent EGFR from binding EGF or signal transduction via the EGF-EGFR pathway. This may have clinical implications for improving treatment based on EGFR targeting in select patients with bladder cancer.
Insights
Interferon-alpha (IFN-alpha) can up-regulate epidermal growth factor receptor (EGFR) expression and inhibit bladder cancer cell growth. This suggests potential for EGFR-targeted therapies in some patients.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Epidermal Growth Factor Receptor (EGFR) is a key target in cancer therapy.
- Interferon-alpha (IFN-alpha) is an immunomodulatory cytokine with anti-cancer properties.
Purpose of the Study:
- To investigate the effect of IFN-alpha on EGFR expression in human bladder cancer cell lines.
- To assess IFN-alpha's impact on cancer cell proliferation and EGF sensitivity.
Main Methods:
- Cell proliferation assessed via crystal violet colorimetric and clonogenic assays.
- EGFR expression quantified using flow cytometry with specific antibodies and ligand binding.
Main Results:
- IFN-alpha (100 IU/ml) modulated cell surface EGFR expression in 8 of 11 bladder cancer cell lines (upregulated in 6, downregulated in 2).
- EGFR overexpression peaked at 48-96 hours, increasing 35%-241% and correlating with intracellular levels.
- IFN-alpha inhibited cell growth in lines with EGFR overexpression, yet cells remained sensitive to EGF.
Conclusions:
- IFN-alpha transiently upregulates EGFR expression and inhibits in vitro growth in select bladder cancer cells.
- IFN-alpha does not impede EGF binding or downstream signaling via the EGF-EGFR pathway.
- Findings suggest potential clinical applications for EGFR-targeted treatments in specific bladder cancer patient populations.
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