Role of secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in prostate cancer progression: Novel biomarker and therapeutic target
| Autor: | Belinda L. Sun, Xiaoguang Sun, Joe G.N. Garcia, Taylor Gregory, Amit M. Algotar, Sara M. Camp, Nancy Casanova, Alexander N. Garcia, Vivian Reyes Hernon, Radu C. Oita, Anne E. Cress |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_treatment Nicotinamide phosphoribosyltransferase lcsh:Medicine urologic and male genital diseases Targeted therapy Prostate cancer chemistry.chemical_compound Mice 0302 clinical medicine Neoplasm Metastasis Aged 80 and over lcsh:R5-920 General Medicine Middle Aged Immunohistochemistry Tumor progression 030220 oncology & carcinogenesis Biomarker (medicine) Cytokines Heterografts Disease Susceptibility lcsh:Medicine (General) Research Paper Enzyme-Linked Immunosorbent Assay General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Downregulation and upregulation In vivo medicine Biomarkers Tumor Animals Humans eNAMPT Aged Neoplasm Staging business.industry lcsh:R Prostatic Neoplasms Muscle Smooth Biomarker medicine.disease Disease Models Animal 030104 developmental biology chemistry ROC Curve Case-Control Studies Cancer research TLR4 Neoplasm Grading business |
| Zdroj: | EBioMedicine, Vol 61, Iss, Pp 103059-(2020) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | Background There remains a serious need to prevent the progression of invasive prostate cancer (PCa). We previously showed that secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a multifunctional innate immunity regulator via TLR4 ligation which has been implicated in PCa progression. Here we investigate the role of eNAMPT as a diagnostic biomarker and therapeutic target in the progression of PCa. Methods Tumor NAMPT expression and plasma eNAMPT level were evaluated in human subjects with various PCa tumor stages and high risk subjects followed-up clinically for PCa. The genetic regulation of NAMPT expression in PCa cells and the role of eNAMPT in PCa invasion were investigated utilizing in vitro and in vivo models. Findings Marked NAMPT expression was detected in human extraprostatic-invasive PCa tissues compared to minimal expression of organ-confined PCa. Plasma eNAMPT levels were significantly elevated in PCa subjects compared to male controls, and significantly greater in subjects with extraprostatic-invasive PCa compared to subjects with organ-confined PCa. Plasma eNAMPT levels showed significant predictive value for diagnosing PCa. NAMPT expression and eNAMPT secretion were highly upregulated in human PCa cells in response to hypoxia-inducible factors and EGF. In vitro cell culture and in vivo preclinical mouse model studies confirmed eNAMPT-mediated enhancement of PCa invasiveness into muscle tissues and dramatic attenuation of PCa invasion by weekly treatment with an eNAMPT-neutralizing polyclonal antibody. Interpretation This study suggests that eNAMPT is a potential biomarker for PCa, especially invasive PCa. Neutralization of eNAMPT may be an effective therapeutic approach to prevent PCa invasion and progression. |
| Databáze: | OpenAIRE |
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