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Expression and Functional Role of ALDH1 in Cervical Carcinoma Cells

  • Rao, Qun-Xian (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Yao, Ting-Ting (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Zhang, Bing-Zhong (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Lin, Rong-Chun (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Chen, Zhi-Liao (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Zhou, Hui (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Wang, Li-Juan (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Lu, Huai-Wu (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Chen, Qin (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Di, Na (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University) ;
  • Lin, Zhong-Qiu (Department of Gynecologic Oncology, Memorial Hospital of SunYat-sen University)
  • Published : 2012.04.30

Abstract

Tumor formation and growth is dictated by a very small number of tumor cells, called cancer stem cells, which are capable of self-renewal. The genesis of cancer stem cells and their resistance to conventional chemotherapy and radiotherapy via mechanisms such as multidrug resistance, quiescence, enhanced DNA repair abilities and anti-apoptotic mechanisms, make it imperative to develop methods to identify and use these cells as diagnostic or therapeutic targets. Aldehyde dehydrogenase 1 (ALDH1) is used as a cancer stem cell marker. In this study, we evaluated ALDH1 expression in CaSki, HeLa and SiHa cervical cancer cells using the Aldefluor method to isolate ALDH1-positive cells. We showed that higher ALDH1 expression correlated with significantly higher rates of cell proliferation, microsphere formation and migration. We also could demonstrate that SiHa-ALDH1-positive cells were significantly more tumorigenic compared to SiHa-ALDH1-negative cells. Similarly, SiHa cells overexpressing ALDH1 were significantly more tumorigenic and showed higher rates of cell proliferation and migration compared to SiHa cells where ALDH1 expression was knocked down using a lentivirus vector. Our data suggested that ALDH1 is a marker of cervical cancer stem cells and expand our understanding of its functional role.

Keywords

References

  1. Charafe-Jauffret E, Ginestier C, Iovino F, et al (2010). Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res, 16, 45-55. https://doi.org/10.1158/1078-0432.CCR-09-1630
  2. Corti S, Locatelli F, Papadimitriou D, et al (2006). Identification of a primitive brain-derived neural stem cell population based on aldehyde dehydrogenase activity. Stem Cells, 24,975-85. https://doi.org/10.1634/stemcells.2005-0217
  3. Croker AK, Goodale D, Chu J, et al (2009). High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med, 13, 2236-52. https://doi.org/10.1111/j.1582-4934.2008.00455.x
  4. Friedman GK, Gillespie GY (2011). Cancer stem cells and pediatric solid tumors. Cancers, 3, 298-318. https://doi.org/10.3390/cancers3010298
  5. Ghaffari S (2011). Cancer, stem cells and cancer stem cells: old ideas, new developments. F1000 Med Rep, 3, 23.
  6. Ginestier C, Wicinski J, Cervera N, et al (2009). Retinoid signaling regulates breast cancer stem cell differentiation. Cell Cycle, 8, 3297-302. https://doi.org/10.4161/cc.8.20.9761
  7. Heerma van Voss MR, van der Groep P, Bart J, van der Wall E, van Diest PJ (2011). Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer. Cell Oncol, 34, 3-10. https://doi.org/10.1007/s13402-010-0007-3
  8. Jiang F, Qiu Q, Khanna A, et al (2009). Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res, 7, 330-8. https://doi.org/10.1158/1541-7786.MCR-08-0393
  9. Kahlert C, Bergmann F, Beck J, et al (2011). Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer. BMC Cancer, 11, 275.
  10. Lapidot T, Sirard C, Vormoor J, et al (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367, 645-8. https://doi.org/10.1038/367645a0
  11. Logan CY, Nusse R (2004). The Wnt signaling pathway in development and disease. Ann Rev Cell Dev Biol, 20, 781- 810. https://doi.org/10.1146/annurev.cellbio.20.010403.113126
  12. Ma S, Chan KW, Lee TK, et al (2008). Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations, Mol Cancer Res, 6, 1146-53. https://doi.org/10.1158/1541-7786.MCR-08-0035
  13. Moody CA, Laimins LA (2010). Human papillomavirus oncoproteins: pathways to transformation. Nature Rev Cancer, 10, 550-60. https://doi.org/10.1038/nrc2886
  14. Moreb JS, Ucar D, Han S, et al (2012). The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. Chem Biol Interact, 195, 52-60. https://doi.org/10.1016/j.cbi.2011.10.007
  15. Moreb JS, Zucali JR, Ostmark B, Benson NA (2007). Heterogeneity of aldehyde dehydrogenase expression in lung cancer cell lines is revealed by Aldefluor flow cytometrybased assay. Cytometry B Clin Cytom, 72, 281-9.
  16. Morimoto K, Kim SJ, Tanei T, et al (2009). Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci, 100, 1062-8. https://doi.org/10.1111/j.1349-7006.2009.01151.x
  17. Park CH, Bergsagel DE, McCulloch EA (1971). Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst, 46, 411-22.
  18. Reya T, Morrison SJ, Clarke MF, Weissman IL (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105-11. https://doi.org/10.1038/35102167
  19. Rice KL, Izon DJ, Ford J, et al (2008). Overexpression of stem cell associated ALDH1A1, a target of the leukemogenic transcription factor TLX1/HOX11, inhibits lymphopoiesis and promotes myelopoiesis in murine hematopoietic progenitors. Leuk Res, 32, 873-83. https://doi.org/10.1016/j.leukres.2007.11.001
  20. Sagar J, Chaib B, Sales K, Winslet M, Seifalian A (2007). Seifalian, Role of stem cells in cancer therapy and cancer stem cells: a review. Cancer Cell Int, 7, 9. https://doi.org/10.1186/1475-2867-7-9
  21. Saini V, Shoemaker RH (2010). Potential for therapeutic targeting of tumor stem cells. Cancer Sci, 101, 16-21. https://doi.org/10.1111/j.1349-7006.2009.01371.x
  22. Schnier JB, Kaur G, Kaiser A, et al (1999). Identification of cytosolic aldehyde dehydrogenase 1 from non-small cell lung carcinomas as a flavopiridol-binding protein. FEBS Lett, 454, 100-4. https://doi.org/10.1016/S0014-5793(99)00773-5
  23. Scholl SM, Kenter G, Kurzeder C, Beuzeboc P (2011). Pathway profiling and rational trial design for studies in advanced stage cervical carcinoma: a review and a perspective. ISRN Oncol, 2011, 403098.
  24. Sophos NA, Vasiliou V (2003). Aldehyde dehydrogenase gene superfamily: the 2002 update. Chem Biol Interact, 143-144, 5-22. https://doi.org/10.1016/S0009-2797(02)00163-1
  25. Stanley M (2010). Pathology and epidemiology of HPV infection in females. Gynecol Oncol, 117, S5-10. https://doi.org/10.1016/j.ygyno.2010.01.024
  26. Storms RW, Green PD, Safford KM, et al (2005). Distinct hematopoietic progenitor compartments are delineated by the expression of aldehyde dehydrogenase and CD34. Blood, 106, 95-102. https://doi.org/10.1182/blood-2004-09-3652
  27. Su Y, Qiu Q, Zhang X, et al (2010). Aldehyde dehydrogenase 1 A1-positive cell population is enriched in tumor-initiating cells and associated with progression of bladder cancer. Cancer Epidemiol Biomarkers Prev, 19, 327-37. https://doi.org/10.1158/1055-9965.EPI-09-0865
  28. Vasiliou V, Pappa A, Petersen DR (2000). Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chem Biol Interact, 129, 1-19. https://doi.org/10.1016/S0009-2797(00)00211-8
  29. Vogler T, Kriegl L, Horst D, et al (2011). The expression pattern of aldehyde dehydrogenase 1 (ALDH1) is an independent prognostic marker for low survival in colorectal tumors. Exp Mol Pathol, 92, 111-7.
  30. Wakamatsu Y, Sakamoto N, Oo HZ, et al (2012). Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int, 62, 112-9. https://doi.org/10.1111/j.1440-1827.2011.02760.x
  31. Walboomers JM, Jacobs MV, Manos MM, et al (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol, 189, 12-9. https://doi.org/10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F
  32. Wang YC, Yo YT, Lee HY, et al (2012). ALDH1-bright epithelial ovarian cancer cells are associated with CD44. Drug resistance, and poor clinical outcome. Am J Pathol, 180, 1159-69. https://doi.org/10.1016/j.ajpath.2011.11.015
  33. Wang Y, Zhe H, Gao P, et al (2011). Cancer stem cell marker ALDH1 expression is associated with lymph node metastasis and poor survival in esophageal squamous cell carcinoma: a study from high incidence area of northern China. Diseases of the Esophagus; doi: 10.1111/j.1442-2050.2011.01279.x
  34. Yao T, Chen Q, Zhang B, Zhou H, Lin Z (2011). The expression of ALDH1 in cervical carcinoma. Med Sci Monit, 17, HY21-26. https://doi.org/10.12659/MSM.881886
  35. Yoshida A, Hsu LC, Dave V (1992). Retinal oxidation activity and biological role of human cytosolic aldehyde dehydrogenase. Enzyme, 46, 239-44.

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