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Two- and three-dimensional cell structures govern epidermal growth factor survival function in human bladder
V Dangles1, F Féménia, V Lainé
1URA INRA-DGER d'Immunopathologie Cellulaire et Moléculaire, Ecole Nationale Vétérinaire, Maisons Alfort, France.
Cancer Research
|August 15, 1997
Summary
Epidermal growth factor (EGF) receptor ligands like EGF affect apoptosis differently in bladder cancer cells. They promote cell death in 2D cultures but prevent it in 3D spheroids, impacting radiotherapy.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Human bladder carcinomas frequently exhibit elevated epidermal growth factor (EGF) receptor expression.
- The role of EGF receptor ligands in bladder cancer cell apoptosis remains incompletely understood, particularly in different culture models.
Purpose of the Study:
- To investigate the differential effects of EGF and transforming growth factor alpha (TGF-α) on apoptosis in human bladder carcinoma cell lines.
- To explore the association between EGF signaling, p21 WAF1/CIP1 expression, and apoptosis in both monolayer and spheroid cultures.
- To assess the potential of blocking EGF signal transduction to enhance radiotherapy efficacy in bladder cancer.
Main Methods:
- Utilized three human bladder carcinoma cell lines (OBR, T24, 647V).
- Cultured cells as both monolayers and three-dimensional (3D) spheroids.
- Administered EGF and TGF-α to serum-starved cells.
- Assessed apoptosis induction and prevention.
- Measured p21 WAF1/CIP1 expression.
- Investigated the effects of genistein and tyrphostin AG1478 on EGF-mediated protection against radiation-induced apoptosis in spheroids.
Main Results:
- EGF and TGF-α enhanced apoptosis in serum-starved monolayer cultures.
- Conversely, EGF and TGF-α prevented apoptosis in serum-starved 3D spheroid cultures.
- Both the enhancement and inhibition of apoptosis by EGF were linked to p21 WAF1/CIP1 overexpression.
- In 647V spheroids, EGF-mediated protection against radiation-induced apoptosis was reversed by genistein and tyrphostin AG1478.
Conclusions:
- EGF receptor ligands exert opposing effects on bladder cancer cell apoptosis depending on the culture dimensionality (monolayer vs. 3D spheroid).
- EGF signaling, involving p21 WAF1/CIP1, plays a critical role in modulating apoptosis in bladder cancer.
- Blocking EGF signal transduction pathways may represent a viable strategy to improve radiotherapy outcomes in bladder cancer patients.