Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis

Abstract

Background:Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear.Methods:ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression.Results:In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated.Conclusions:We report here the association of ALDH3A1 with PC progression.

Expression and regulation of aldehyde dehydrogenases in prostate cancer

“…the ALDH1A1 isoform positively correlates with the expression of CSC surface markers CD133 [116] and CD34 [117] with utility in characterising liver CSCs and leukaemia SCs, respectively. The association of ALDH3A1 has also been reported in PCa progression [61] . Stem cell-like cells from DU145 cells have elevated expression of ALDH3A1 compared to non-stem counterparts, and the stem cell-like population generated xenograft tumours with aggressive features [118] .…”

“…In PCa, several ALDH isoforms (1A1, 1A3, 3A1, 3A2, 4A1, 7A1, 9A1 and 18A1) have been found to be overexpressed [15,[60][61][62][63][64][65][66][67][68] , but only a few isoforms appear to play critical roles in PCa. In a recent proteomic study [69] , ALDH1A3 expression was in part controlled via miR-187, as downregulation of this microRNA led to induction of ALDH1A3, while re-introduction decreased ALDH1A3 expression in PC-3, DU145 and LNCAP prostate cancer cells.…”

“…Outside the ALDH1 family, strong association of ALDH3A1 with PCa progression has also been demonstrated in both immortalised cancer cell lines and tumour xenografts [61] . In clinical tissues ALDH3A1 was detected in intra-epithelial neoplasia, with elevated levels in carcinomas in the absence of expression in normal prostate glands.…”

Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

“…Multiple isoforms were studied and it was found that the ALDH3A1 enzyme displays the most drastic upregulation, though ALDH1A3, ALDH2, ALDH3A2, ALDH3B1, ALDH5A1, ALDH19A1, ALDH16A1 and ALDH18A1 were also upregulated [152]. Besides its role in lipid-peroxidation, an increase in ALDH3A1 has been shown to be associated with prostate carcinoma where increased level of ALDH3A1 correlated with an increased severity of prostate cancer [160]. …”

Pyranocoumarin Tissue Distribution, Plasma Metabolome and Prostate Transcriptome Impacts of Sub-Chronic Exposure to KoreanAngelicaSupplement in Mice

“…The protein level of brown fat-specific Ucp 1 (uncoupling protein 1) increases with disease progression from normal tissue, primary cancer to bone metastases (Zhau et al, 2011). Alah3a1 (Aldehyde dehydrogenase 3A1) was reported to correlate with the progression of prostate cancer in human, and in vitro and animal studies confirmed a robust up-regulation of Aldh3a1 in human DU145-derived cancer stem cells (Yan et al, 2014). Foxa1 (detected by qRT-PCR, Fig.…”