Expression of stem cell biomarker aldehyde dehydrogenase 1 (ALDH1) in canine mammary tumor

D S GAVHANE; A SINGH; N K SOOD; K GUPTA

doi:10.56093/ijans.v86i3.56650

Authors

D S GAVHANE Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab 141 001 India
A SINGH Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab 141 001 India
N K SOOD Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab 141 001 India
K GUPTA Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab 141 001 India

https://doi.org/10.56093/ijans.v86i3.56650

Keywords:

ALDH1, Canine mammary tumor, Immunohistochemistry, Stem cell

Abstract

The study was conducted to investigate the immunohistochemical expression of a stem cell biomarker, ALDH1 in CMTs. ALDH1 is a cytosolic enzyme responsible for oxidizing intracellular aldehydes leading to the oxidation of retinol to retinoic acid, a key step involved in early stem cell differentiation. It was noticed that the cells expressing this marker possess ability to self renew. In present investigation, we assessed the expression of ALDH1 by immunohistochemistry on paraffin embedded tissue sections from 31 confirmed clinical cases of canine mammary tumors (CMT). The results of immunohistochemistry were analyzed semiquantitatively by calculating percentage score and staining intensity using light microscope and comparing it with the histological types. ALDH1 expression was detected in 26 (83%) of CMTs and it was observed in benign lesions, invasive cells and cells undergoing epithelial to mesenchymal transition (EMT). The high expression patterns of ALDH1 in various histological types of CMT indicated poor prognosis.

Downloads

Download data is not yet available.

References

Al-Hajj M and Clarke M F. 2004. Self-renewal and solid tumor stem cells. Oncogene 23: 7274–82. DOI: https://doi.org/10.1038/sj.onc.1207947

Antuofermo E, Miller M A, Pirino S, Xie J, Badve, S and Mohammed S L 2007. Spontaneous mammary intraepithelial lesions in dogs: A model of breast cancer. Cancer Epidemiology 16: 2247–56. DOI: https://doi.org/10.1158/1055-9965.EPI-06-0932

Burger P E, Gupta R, Xiong X, Ontiveros C S, Salm S N, Moscatelli D and Wilson E L. 2009. High ALDH activity: A novel functional marker of murine prostate stem/progenitor cells. Stem Cells 27 (9): 2220–28. DOI: https://doi.org/10.1002/stem.135

Chaw S Y, Majeed A A, Dalley A J, Chan A, Stein S and Farah C S. 2012. Epithelial to mesenchymal transition (EMT) biomarkers—E-cadherin, beta-catenin, APC and Vimentin— in oral squamous cell carcinogenesis and transformation. Oral Oncology 48 (10): 997–1006. DOI: https://doi.org/10.1016/j.oraloncology.2012.05.011

Clarke M F, Dick J E, Dirks P B, Eaves C J, Jamieson C H, Jones D L, Visvader J, Weissman I L and Wahl G M. 2006. Cancer stem cells-perspectives on current status and future directions: AACR workshop on cancer stem cells. Cancer Research 66: 9339 –44. DOI: https://doi.org/10.1158/0008-5472.CAN-06-3126

Croker A K, Goodale D, Chu J, Postenka C, Hedley B D, Hess D A and Allan A L. 2009. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. Journal of Cellular and Molecular Medicine 13: 2236 –52. DOI: https://doi.org/10.1111/j.1582-4934.2008.00455.x

Douville J, Beaulieu R and Balicki D. 2009. ALDH1 as a functional marker of cancer stem and progenitor cells. Stem Cells and Development 18:17–26. DOI: https://doi.org/10.1089/scd.2008.0055

Ely K A, Carter B A, Jensen R A, Simpson J F and Page D L. 2001. Core biopsy of the breast with atypical ductal hyperplasia: a probabilistic approach to reporting. American Journal of Surgical Pathology 25:1017–21. DOI: https://doi.org/10.1097/00000478-200108000-00005

Fillmore C M and Kuperwasser C. 2008. Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Research 10: R25. DOI: https://doi.org/10.1186/bcr1982

Ginestier C, Hur M H, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer C G, Liu S, Schott A, Hayes D, Birnbaum D, Wicha M S and Dontu G. 2007. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1: 555–67. DOI: https://doi.org/10.1016/j.stem.2007.08.014

Hendrix M J C, Seftor E A, Seftor R E B, Kasemeier-Kulesa P M and Postovit L. 2007. Reprogramming metastatic tumor cells with embryonic microenvironments. Nature Reviews Cancer 7: 246–55. DOI: https://doi.org/10.1038/nrc2108

Kallergi G, Papadaki M A, Dimitris E P, Georgoulias M V and Agelaki S. 2011. Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Research 13 (3): R59. DOI: https://doi.org/10.1186/bcr2896

Kretschmer C, Sterner-Kock A, Siedentopf F, Schoenegg W, Schlag P M, and Kemmner W. 2011. Identification of early molecular markers for breast cancer. Molecular Cancer 10: 15. DOI: https://doi.org/10.1186/1476-4598-10-15

Ma I and Allan A L. 2011. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Reviews and Reports 7: 292 –306. DOI: https://doi.org/10.1007/s12015-010-9208-4

Mediana D. 2008. Premalignant and malignant mammary lesions Induced by MMTV and chemical carcinogens. Journal of Mammary Gland Biology and Neoplasia 13:271–27. DOI: https://doi.org/10.1007/s10911-008-9086-4

Misdorp W. 2002. Tumours of the mammary gland. Tumors in Domestic Animals. 4th edn, pp.575–606. (Ed.) Meuten D J. Iowa State Press, Blackwell Publishing Company, U.K. DOI: https://doi.org/10.1002/9780470376928.ch12

Savagner P P. 2010. The epithelial-mesenchymal transition (EMT) phenomenon. Annals of Oncology 21 (7): 89–92. DOI: https://doi.org/10.1093/annonc/mdq292

Schmitt J F, Keogh M C, Dennehy U, Chen D, Lupu F, Weston K, Taylor F, Kakkar V and Lemoine N R. 1999. Tissue-selective expression of dominant-negative proteins for the regulation of vascular smooth muscle cell proliferation. Gene Therapy 6: 1184–91. DOI: https://doi.org/10.1038/sj.gt.3300927

Sorenmo K. 2003. An update on canine mammary gland tumors. ACVIM Forum Proceedings 16: 387–88.

Tanei T, Morimoto K, Shimazu K, Kim S J, Tanji Y, Taguchi T, Tamaki Y and Noguchi S. 2009. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential Paclitaxel and epirubicin-based chemotherapy for breast cancers. Clinical Cancer Research 15: 4234–41. DOI: https://doi.org/10.1158/1078-0432.CCR-08-1479

Visvader J E. 2009. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes and Development 23: 2563–77. DOI: https://doi.org/10.1101/gad.1849509