Overexpression and surface localization of HPRT in prostate cancer provides a potential target for cancer specific antibody mediated cellular cytotoxicity
| Autor: | Eliza E. Bitter, Richard A. Robison, Abigail M. Felsted, Kim L. O'Neill, Kelsey B. Bennion, Michelle H. Townsend |
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| Rok vydání: | 2021 |
| Předmět: |
Cytotoxicity
Immunologic Male 0301 basic medicine Hypoxanthine Phosphoribosyltransferase cells genetic processes Cell Line Flow cytometry 03 medical and health sciences Prostate cancer 0302 clinical medicine DU145 medicine Humans Antibody-dependent cell-mediated cytotoxicity medicine.diagnostic_test biology Cell Membrane Prostatic Neoplasms nutritional and metabolic diseases Cancer Cell Biology medicine.disease enzymes and coenzymes (carbohydrates) 030104 developmental biology Hypoxanthine-guanine phosphoribosyltransferase 030220 oncology & carcinogenesis Cancer cell Cancer research biology.protein Tumor Suppressor Protein p53 Antibody Cell Division |
| Zdroj: | Experimental Cell Research. 403:112567 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2021.112567 |
| Popis: | We chose to evaluate Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) as a possible biomarker for prostate cancer due to its involvement in nucleotide synthesis and cell cycle progression. We utilized two prostate cancer cell lines (PC3 and DU145) along with patient tissue and knockdowns to evaluate overall HPRT expression. The surface localization of HPRT was determined utilizing flow cytometry, confocal microscopy, and scanning electron microscopy followed by ADCC to evaluate targeting potential. We found significant upregulation of HPRT within malignant samples with approximately 47% of patients had elevated levels of HPRT compared to normal controls. We also observed a significant association between HPRT and the plasma membrane of DU145 cells (p = 0.0004), but found no presence on PC3 cells (p = 0.14). This was confirmed with scanning electron microscopy and confocal microscopy. ADCC experiments were performed to determine whether HPRT could be used as a target antigen for selective cell-mediated killing. We found that DU145 cells treated with HPRT antibodies had a significantly higher incidence of cell death than both isotype treated samples and PC3 cells treated with the same concentrations of HPRT antibody. Finally, we determined that p53 had a significant impact on HPRT expression both internally and on the surface of cancer cells. These results suggest HPRT as a possible biomarker target for the treatment of patients with prostate cancer. |
| Databáze: | OpenAIRE |
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