Iranian Journal of Pathology

Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells

Document Type : Original Research

Authors

Ali-Ahmad Bayat 1
Niloufar Sadeghi 1
Ghazaleh Fazli 1
Mohammad Reza Nowroozi 2
Solmaz Ohadian Moghadam 2
Amin Radmanesh 3
Mohammadjavad Hedayatshodeh 3
Ali Reza Sarrafzadeh 4
Omid Zarei 5
Fatemeh Ghaemimanesh 1
Hodjattallah Rabbani 1

1 Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran

2 Uro-Oncology Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

4 Department of Pathology, Khatam Al Anbia Hospital, Tehran, Iran

5 Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

https://doi.org/10.30699/ijp.2022.539411.2732
Abstract
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.

Highlights

  • A high level of sortilin expression was observed in primary bladder carcinoma tissues and cell lines in comparison with the normal bladder tissues and normal cell line
  • Anti-sortilin mAb induced apoptosis in EJ138 and 5637 bladder cancer cells without any significant effect on the normal control cell line
  • Sortilin may represent a potential candidate for targeted therapy in patients with bladder carcinoma

Keywords

Bladder cancer
Flow cytometry
Monoclonal antibody
Sortilin

Subjects

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Iranian Journal of Pathology
Volume 17, Issue 2
Spring 2022
Pages 174-182

  • Receive Date 21 September 2021
  • Revise Date 30 November 2021
  • Accept Date 17 December 2021

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