Neuroendocrine differentiation of prostate cancer leads to PSMA suppression
| Autor: | Yinan Li, Cheol Kwak, Lisa A. Porter, Abdulkadir Hussein, Yuzhuo Wang, Hyewon Youn, Xuesen Dong, Keon Wook Kang, Alastair D. Lamb, Chang Wook Jeong, Gi Jeong Cheon, Mohamadreza K. Bakht, Iulian Derecichei, Rosa Maria Ferraiuolo, Mark J Dunning, Keith F. Stringer, So Won Oh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research Endocrinology Diabetes and Metabolism Cellular differentiation Biology Neuroendocrine differentiation 030218 nuclear medicine & medical imaging 03 medical and health sciences chemistry.chemical_compound Prostate cancer 0302 clinical medicine Endocrinology medicine Humans Somatostatin receptor 2 Enzalutamide Somatostatin receptor Prostatic Neoplasms Cell Differentiation Prostate-Specific Antigen medicine.disease Oncology chemistry Cell culture 030220 oncology & carcinogenesis Disease Progression Cancer research Hormone |
| Zdroj: | Endocrine-Related Cancer. 26:131-146 |
| ISSN: | 1479-6821 1351-0088 |
| Popis: | Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression ofFOLH1, NEPC marker genes andSSTR2. We evaluated the transcript abundance forFOLH1andSSTR2genes as well as NE markers across 909 tumors. A significant suppression ofFOLH1in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression ofFOLH1and amplification ofSSTR2expression. Due to the observedFOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation ofSSTR2in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|