Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis.
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.
1] Division of Nephrology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8 [2] Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6 [3] The Hamilton Center for Kidney Research, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
J
J
Yan
1] Division of Nephrology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8 [2] Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6 [3] The Hamilton Center for Kidney Research, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
J
J
De Melo
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8.
J-C
JC
Cutz
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8.
T
T
Aziz
1] Division of Nephrology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L8 [2] Father Sean O'Sullivan Research Centre, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6 [3] The Hamilton Center for Kidney Research, St. Joseph's Healthcare Hamilton, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
D
D
Tang
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology; D000444:Aldehyde Dehydrogenase / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D000728:Androgens; D000818:Animals; D001859:Bone Neoplasms / Q000201:enzymology / Q000556:secondary; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000201:enzymology; D019048:Prostatic Intraepithelial Neoplasia / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology
D000728:Androgens; D009363:Neoplasm Proteins; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase