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Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells
Ali-Ahmad Bayat1, Niloufar Sadeghi1, Ghazaleh Fazli1
1Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
Background & Objective:
Cell surface expression of sortilin in different types of cancer signifies it as a therapeutic target for cancer therapy. The aim of this study was to detect sortilin expression in bladder cancer cells using an anti-sortilin monoclonal antibody (mAb) to evaluate sortilin as a target for developing diagnostic and therapeutic agents against bladder carcinoma.
Methods:
The protein expression of sortilin in bladder cancer tissues and cell lines (5637 and EJ138) was investigated by immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry. Furthermore, the capability of anti-sortilin mAb in apoptosis induction in bladder cancer cells was evaluated.
Results:
A high expression level was observed in bladder carcinoma tissues (P≤0.001) and cell lines, using IHC and ICC, respectively. Flow cytometry results showed cell surface expression of 27.5±3% (P≤0.01), 74.4±7.8% (P≤0.001), and 4.2±0.4% of sortilin in EJ138, 5637, and HFFF cells, respectively. In EJ138 anti-sortilin mAb induced apoptosis in 25.2±11.5% (P≤0.05) (early) and 4.5±1.1% (P>0.05) (late) after 6 h incubation, while for 12 h, the values of 11.6±3.8% (P>0.05) and 20.7±4.4% (P≤0.05) were achieved. In 5637 cells, 6 h incubation resulted in 10.2±0.3% (P>0.05) and 6.6±1.4% (P>0.05) apoptosis induction, while these values were 12.1±0.8% (P>0.05) and 27.4±4.5% (P≤0.01) after 12 h. The HFFF cells did not show significant apoptosis.
Conclusion:
The overexpression of sortilin in bladder tumor cells and its potential in inducing apoptosis via directed targeting with the specific monoclonal antibody may represent this protein as a potential candidate of targeted therapy in bladder carcinoma.
Insights
Sortilin is highly expressed in bladder cancer, making it a promising therapeutic target. An anti-sortilin monoclonal antibody effectively induced apoptosis in bladder cancer cells, suggesting potential for targeted therapy.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Sortilin, a protein, is expressed on the cell surface in various cancers.
- Its expression suggests sortilin is a potential therapeutic target for cancer treatment.
Purpose of the Study:
- To detect sortilin expression in bladder cancer cells.
- To evaluate sortilin as a target for diagnostic and therapeutic agents against bladder carcinoma using an anti-sortilin monoclonal antibody (mAb).
Main Methods:
- Investigated sortilin protein expression in bladder cancer tissues and cell lines (5637, EJ138) using immunohistochemistry (IHC), immune-cytochemistry (ICC), and flow cytometry.
- Assessed the capability of anti-sortilin mAb to induce apoptosis in bladder cancer cells.
Main Results:
- High sortilin expression was observed in bladder carcinoma tissues and cell lines (P≤0.001).
- Flow cytometry revealed significant cell surface sortilin expression in EJ138 (27.5±3%, P≤0.01) and 5637 (74.4±7.8%, P≤0.001) cells.
- Anti-sortilin mAb induced apoptosis in EJ138 and 5637 cells, with varying percentages at 6 and 12 hours (P≤0.05 for several conditions).
Conclusions:
- Overexpression of sortilin in bladder tumor cells was confirmed.
- Targeting sortilin with a specific monoclonal antibody demonstrated potential for inducing apoptosis.
- Sortilin represents a potential candidate for targeted therapy in bladder carcinoma.
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