Hypoxia-induced angiopoietin-like protein 4 as a clinical biomarker and treatment target for human prostate cancer
| Autor: | Kazunori Iwasaki, Takeo Nomura, Fuminori Sato, Shinro Hata, Ryuta Sato, Hiromitsu Mimata, Mutsushi Yamasaki |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine PCA3 Cancer Research Antineoplastic Agents Apoptosis Docetaxel Angiopoietin-like 4 Protein Biology medicine.disease_cause 03 medical and health sciences Prostate cancer 0302 clinical medicine Cell Movement LNCaP Tumor Cells Cultured medicine Angiopoietin-Like Protein 4 Humans RNA Small Interfering Hypoxia Protein kinase B PI3K/AKT/mTOR pathway Aged Cell Proliferation Oncogene Prostatic Neoplasms General Medicine Middle Aged Prognosis medicine.disease 030104 developmental biology Oncology Drug Resistance Neoplasm Case-Control Studies 030220 oncology & carcinogenesis Cancer research Taxoids Carcinogenesis Biomarkers Signal Transduction |
| Zdroj: | Oncology Reports. 38:120-128 |
| ISSN: | 1791-2431 1021-335X |
| Popis: | Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional protein, playing roles in glucose and lipid metabolism, inflammation, angiogenesis, and tumorigenesis. Recent research suggests that ANGPTL4 is induced by hypoxia and is a useful diagnostic or prognostic marker for various cancers. However, it remains unclear whether ANGPTL4 expression influences prostate cancer. Here we examined the biological and clinical relevance of ANGPTL4 expression in prostate cancer. Firstly we examined ANGPTL4 expression in the prostate cancer cell lines LNCaP and LNCaP/CH incubated at 1% O2 for at least 6 months. We compared cellular proliferation, migration, and ANGPTL4 secretion in a culture medium between these cell lines. In addition, we investigated the effect of various concentrations of recombinant ANGPTL4 protein (rANGPTL4) on cellular proliferation and intracellular signaling pathways. Moreover, we used ANGPTL4 knockdown by RNA interference to investigate the influence of ANGPTL4 expression on these cell lines. Finally, we investigated the correlation between ANGPTL4 expression in prostate cancer specimens and clinicopathological parameters using immunohistochemistry. Our data suggested that the expression of ANGPTL4 in hypoxic conditions was 14.4-fold higher than that in normoxic condition. ANGPTL4 secretion in the culture medium increased 7.0-fold. In addition, rANGPTL4 increased cellular proliferation 1.72-fold via Akt activation. Moreover, ANGPTL4 knockdown decreased cell growth and its secretion by 25.7 and 41.4%, respectively, compared with the control. A multivariate analysis showed that positive ANGPTL4 expression in the resected specimens was an independent prognostic indicator of biochemical recurrence (P=0.03, hazard ratio = 2.02). Our results show that ANGPTL4 is induced by hypoxia and promotes cancer progression via the activated PI3K/Akt pathway. Moreover, ANGPTL4 can be used as a prognostic marker for prostate cancer patients undergoing radical prostatectomy. |
| Databáze: | OpenAIRE |
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