DOI QR코드

DOI QR Code

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

  • Keymoosi, Hossein (Department Pathology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences) ;
  • Gheytanchi, Elmira (Oncopatholgy Research Centre, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences) ;
  • Asgari, Mojgan (Department Pathology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences) ;
  • Shariftabrizi, Ahmad (Department of Pathology, Tufts University School of Medicine) ;
  • Madjd, Zahra (Department Pathology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences)
  • 발행 : 2014.03.01

초록

Background: The aldehyde dehydrogenase 1 family member A1 (ALDH1A1) is one of the promising markers for identifying cancer stem cells in many cancer types, along with other markers including CD44. The aim of the present study was to evaluate the expression and clinical significance of putative cancer stem cell markers, CD44 and ALDH1A1, in a series of urothelial carcinomas of urinary bladder (UCUB) by tissue microarray (TMA). Materials and Methods: A total of 159 Urothelial Carcinomas (UC) including 96 (60%) low grade and 63 (40%) high grade carcinomas were immunohistochemically examined for the expression of CD44 and ALDH1A1. Correlations of the relative expression of these markers with clinicopathological parameters were also assessed. Results: High level expression of ALDH1A1 was found in 16% (25/159) of bladder UC which was significantly correlated with increased tumor size (p value=0.002), high grade (p value<0.001), pathologic stage (T1, p value=0.007 and T2, p value<0.001) and increased rate of recurrence (p value=0.013). A high level of CD44 expression was found in 43% (68/159) of cases, being positively correlated with histologic grade (p value=0.032) and recurrence (p value=0.039). Conclusions: Taken together, our results showed that ALDH1 was concurrently expressed in a fraction of CD44+ tumors and its expression correlated with poor prognosis in UCs. ALDH1A1 could be an ideal marker for targeted therapy of UCs in combination with conventional therapies, particularly in patients with high grade carcinomas. These findings indicate that cells expressing ALDH1A1 along with CD44 can be a potential therapeutic target in bladder carcinomas.

키워드

참고문헌

  1. Ahmad MR, Pervaiz MK, Pervaiz (2012). Non-occupational risk factors of urinary bladder cancer in Faisalabad and Lahore, Pakistan. J Pak Med Assoc, 62, 236-39.
  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 100, 3983-8. https://doi.org/10.1073/pnas.0530291100
  3. Balicki D (2007). Moving Forward in Human Mammary Stem Cell Biology and Breast Cancer Prognostication Using ALDH1. Cell Stem Cell, 1, 485-7. https://doi.org/10.1016/j.stem.2007.10.015
  4. Bao S, Wu Q, McLendon RE, et al (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature, 444, 756-60. https://doi.org/10.1038/nature05236
  5. Bentivegna A, Conconi D, Panzeri E, et al (2010). Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples. Cancer Sci, 101, 416-24. https://doi.org/10.1111/j.1349-7006.2009.01414.x
  6. Billerey C, Chopin D, Aubriot-Lorton MH, et al (2001). Frequent FGFR3 mutations in papillary non-invasive bladder (pTa) tumors. Am J Pathol, 158, 1955-59. https://doi.org/10.1016/S0002-9440(10)64665-2
  7. Black WJ, Stagos D, Marchitti SA, et al (2009). Human aldehyde dehydrogenase genes: alternatively spliced transcriptional variants and their suggested nomenclature. Pharmacogenet Genomics, 19, 893-902. https://doi.org/10.1097/FPC.0b013e3283329023
  8. Bohl SR, Pircher A, Hilbe W (2011) Cancer stem cells: characteristics and their potential role for new therapeutic strategies. Onkologie, 34, 269-74. https://doi.org/10.1159/000327815
  9. Brandt WD, Matsui W, Rosenberg JE, et al (2009). Urothelial carcinoma: stem cells on the edge. Cancer Metastasis Rev, 28, 291-304. https://doi.org/10.1007/s10555-009-9187-6
  10. Camp RL, Charette LA, Rimm DL (2000). Validation of tissue microarray technology in breast carcinoma. Lab Invest, 80, 1943-9. https://doi.org/10.1038/labinvest.3780204
  11. Chan KS, Espinosa I, Chao M, et al (2009). Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc Natl Acad Sci U S A, 106, 14016-21. https://doi.org/10.1073/pnas.0906549106
  12. Chan KS, Volkmer JP, Weissman I (2010). Cancer stem cells in bladder cancer: a revisited and evolving concept. Curr Opin Urol, 20, 393-97. https://doi.org/10.1097/MOU.0b013e32833cc9df
  13. Chang CC, Shieh GS, Wu P, et al (2008). Oct-3/4 expression reflects tumor progression and regulates motility of bladder cancer cells. Cancer Res, 68, 6281-91. https://doi.org/10.1158/0008-5472.CAN-08-0094
  14. Cheng LR, Montironi R, Davidson DD, Lopez-Beltran A, et al (2009). Staging and reporting of urothelial carcinoma of the urinary bladder. Mod Pathol, 22, 70-95. https://doi.org/10.1038/modpathol.2009.1
  15. Choi D, Lee HW, Hur KY, et al (2009). Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma. World J Gastroenterol, 15, 2258-64. https://doi.org/10.3748/wjg.15.2258
  16. Clarke MF, Dick JE, Dirks PB, et al (2006). Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res, 66, 9339-44. https://doi.org/10.1158/0008-5472.CAN-06-3126
  17. Clay MR, Tabor M, Owen JH, et al (2010). Single-marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck, 32, 1195-201. https://doi.org/10.1002/hed.21315
  18. Cordon-Cardo C, Zhang ZF, Dalbagni G, et al (1997). Cooperative effects of p53 and pRB alterations in primary superficial bladder tumors. Cancer Res, 57, 1217-21.
  19. Cote RJ, Dunn MD, Chatterjee SJ, et al (1998). Elevated and absent pRb expression is associated with bladder cancer progression and has cooperative effects with p53. Cancer Res, 58, 1090-4.
  20. Deng S, Yang X, Lassus H, et al (2010). Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One, 5, 10277. https://doi.org/10.1371/journal.pone.0010277
  21. Dwyer RM, Potter-Beirne SM, Harrington KA, et al (2007). Monocyte chemotactic protein-1 secreted by primary breast tumors stimulates migration of mesenchymal stem cells. Clin Cancer Res, 13, 5020-7. https://doi.org/10.1158/1078-0432.CCR-07-0731
  22. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  23. Ferris J, Berbel O, Alonso-Lopez J, Garcia J, Ortega JA (2013). Environmental non-occupational risk factors associated with bladder cancer. Acta Urol Esp, 37, 579-86.
  24. Ginestier C, Hur MH, Charafe-Jauffret E, et al (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. https://doi.org/10.1016/j.stem.2007.08.014
  25. Grignon DJ (2009). The current classification of urothelial neoplasms. Mod Pathol, 22, 60-9. https://doi.org/10.1038/modpathol.2008.235
  26. Hatina J, Schulz WA (2012). Stem cells in the biology of normal urothelium and urothelial carcinoma. Neoplasma, 59, 728-36. https://doi.org/10.4149/neo_2012_089
  27. He X, Marchionni L, Hansel DE, et al (2009). Differentiation of a highly tumorigenic basal cell compartment in urothelial carcinoma. Stem Cells, 27, 1487-95. https://doi.org/10.1002/stem.92
  28. Heppner GH (1984). Tumor heterogeneity. Cancer Res, 44, 2259-65.
  29. Ho PL, Kurtova A, Chan KS (2012). Normal and neoplastic urothelial stem cells: getting to the root of the problem. Nat Rev Urol, 9, 583-94. https://doi.org/10.1038/nrurol.2012.142
  30. Huang EH, Hynes MJ, Zhang T, et al (2009). Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res, 69, 3382-9. https://doi.org/10.1158/0008-5472.CAN-08-4418
  31. Immervoll H, Hoem D, Sakariassen PO, Steffensen OJ, Molven A (2008). Expression of the “stem cell marker” CD133 in pancreas and pancreatic ductal adenocarcinomas. BMC Cancer, 8, 48. https://doi.org/10.1186/1471-2407-8-48
  32. Immervoll H, Hoem D, Steffensen OJ, Miletic H, Molven A (2011). Visualization of CD44 and CD133 in normal pancreas and pancreatic ductal adenocarcinomas: non-overlapping membrane expression in cell populations positive for both markers. J Histochem Cytochem, 59, 441-55. https://doi.org/10.1369/0022155411398275
  33. Jaggupilli A, Elkord E (2012). Significance of CD44 and CD24 as cancer stem cell markers: an enduring ambiguity. Clin Dev Immunol, 2012, 1-11.
  34. 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
  35. Jordan CT, Guzman ML, Noble M (2006). Cancer stem cells. N Engl J Med, 355, 1253-61. https://doi.org/10.1056/NEJMra061808
  36. Kim YJ, Yoon HY, Kim JS, et al (2013). HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: array-based DNA methylation and expression profiling. Int J Cancer, 133, 1135-42. https://doi.org/10.1002/ijc.28121
  37. Komuro H, Saihara R, Shinya M, et al (2007). Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines. J Pediatr Surg, 42, 2040-5. https://doi.org/10.1016/j.jpedsurg.2007.08.026
  38. Kononen J, Bubendorf L, Kallioniemi A, et al (1998). Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med, 4, 844-7. https://doi.org/10.1038/nm0798-844
  39. Lee HJ, Choe G, Jheon S, et al (2010). CD24, a novel cancer biomarker, predicting disease-free survival of non-small cell lung carcinomas: a retrospective study of prognostic factor analysis from the viewpoint of forthcoming (seventh) new TNM classification. J Thorac Oncol, 5, 649-57.
  40. Li T, Su Y, Mei Y, et al (2010). ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome. Lab Invest, 90, 234-44. https://doi.org/10.1038/labinvest.2009.127
  41. Li X, Lewis MT, Huang J, et al (2008). Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst, 100, 672-9. https://doi.org/10.1093/jnci/djn123
  42. Lingala S, Cui YY, Chen X, et al (2010). Immunohistochemical staining of cancer stem cell markers in hepatocellular carcinoma. Exp Mol Pathol, 89, 27-35. https://doi.org/10.1016/j.yexmp.2010.05.005
  43. Liu DY, Ren CP, Yuan XR, et al (2012). ALDH1 expression is correlated with pathologic grade and poor clinical outcome in patients with astrocytoma. J Clin Neurosci, 19, 1700-5. https://doi.org/10.1016/j.jocn.2012.01.036
  44. Lugli A, Iezzi G, Hostettler I, et al (2010). Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer, 103, 382-90. https://doi.org/10.1038/sj.bjc.6605762
  45. Luo Y, Cui XH, Jiang YG, et al (2012). Sorting and identification of cancer stem cells in human prostate cancer cell lines. Zhonghua Nan Ke Xue, 18, 1062-8.
  46. Madjd Z, Gheytanchi E, Erfani E, Asadi-Lari M (2013). Application of stem cells in targeted therapy of breast cancer: a systematic review. Asian Pac J Cancer Prev, 14, 2789-800. https://doi.org/10.7314/APJCP.2013.14.5.2789
  47. McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS, Sr (1985). Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med, 109, 716-21.
  48. Mehrazma M, Madjd Z, Kalantari E, et al. (2013). Expression of Stem Cell Markers, CD133 and CD44, in Pediatric Solid Tumors: A Study Using Tissue Microarray. Fetal Pediatr Pathol, 32, 192-204. https://doi.org/10.3109/15513815.2012.701266
  49. Mohsenzadegan M, Madjd Z, Asgari M, et al (2013). Reduced expression of NGEP is associated with high-grade prostate cancers: a tissue microarray analysis. Cancer Immunol Immunother, 62, 1609-18. https://doi.org/10.1007/s00262-013-1463-1
  50. Naor D, Wallach-Dayan SB, Zahalka MA, Sionov RV (2008). Involvement of CD44, a molecule with a thousand faces, in cancer dissemination. Semin Cancer Biol, 18, 260-67. https://doi.org/10.1016/j.semcancer.2008.03.015
  51. Overdevest JB, Thomas S, Kristiansen G, et al (2011). CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization. Cancer Res, 71, 3802-11. https://doi.org/10.1158/0008-5472.CAN-11-0519
  52. Pearce DJ, Taussig D, Simpson C, et al (2005). Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells, 23, 752-60. https://doi.org/10.1634/stemcells.2004-0292
  53. Rasheed ZA, Yang J, Wang Q, et al (2010). Prognostic significance of tumorigenic cells with mesenchymal features in pancreatic adenocarcinoma. J Natl Cancer Inst, 102, 340-51. https://doi.org/10.1093/jnci/djp535
  54. 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
  55. Salehi A, Khezri AA, Malekmakan L, Aminsharifi A (2011). Epidemiologic status of bladder cancer in Shiraz, southern Iran. Asian Pac J Cancer Prev, 12, 1323-27.
  56. Satpute PS, Hazarey V, Ahmed R, Yadav L (2013). Cancer stem cells in head and neck squamous cell carcinoma: a review. Asian Pac J Cancer Prev, 14, 5579-87. https://doi.org/10.7314/APJCP.2013.14.10.5579
  57. Slomiany MG, Dai L, Tolliver LB, et al (2009). Inhibition of Functional Hyaluronan-CD44 Interactions in CD133-positive Primary Human Ovarian Carcinoma Cells by Small Hyaluronan Oligosaccharides. Clin Cancer Res, 15, 7593-601. https://doi.org/10.1158/1078-0432.CCR-09-2317
  58. 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
  59. Taeb J, Asgari M, Abolhasani M, Farajollahi MM, Madjd Z (2014). Expression of prostate stem cell antigen (PSCA) in prostate cancer: A tissue microarray study of Iranian patients. Pathol Res Pract, 210, 18-23. https://doi.org/10.1016/j.prp.2013.09.012
  60. Tanei T, Morimoto K, Shimazu K, et al (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. Clin Cancer Res, 15, 4234-41. https://doi.org/10.1158/1078-0432.CCR-08-1479
  61. Urakami S, Shiina H, Enokida H, et al (2006). Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/betacatenin signaling pathway. Clin Cancer Res, 12, 383-91. https://doi.org/10.1158/1078-0432.CCR-05-1344
  62. van Rhijn BW, Montironi R, Zwarthoff EC, Jobsis AC, van der Kwast TH (2002). Frequent FGFR3 mutations in urothelial papilloma. J Pathol, 198, 245-51. https://doi.org/10.1002/path.1202
  63. Wielenga VJ, Heider KH, Offerhaus GJ, et al (1993). Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res, 53, 4754-6.
  64. Woodman AC, Sugiyama M, Yoshida K et al (1996). Analysis of anomalous CD44 gene expression in human breast, bladder, and colon cancer and correlation of observed mRNA and protein isoforms. Am J Pathol, 149, 1519-30.
  65. Wu XR (2005). Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer, 5, 713-25. https://doi.org/10.1038/nrc1697
  66. Yang YM, Chang JW (2008). Bladder cancer initiating cells (BCICs) are among EMA-CD44v6+ subset: novel methods for isolating undetermined cancer stem (initiating) cells. Cancer Invest, 26, 725-33. https://doi.org/10.1080/07357900801941845
  67. Zhang AM, Fan Y, Yao Q, et al (2012). Identification of a cancer stem-like population in the Lewis lung cancer cell line. Asian Pac J Cancer Prev, 13, 761-66. https://doi.org/10.7314/APJCP.2012.13.3.761

피인용 문헌

  1. Expression of Neuronal Markers, NFP and GFAP, in Malignant Astrocytoma vol.15, pp.15, 2014, https://doi.org/10.7314/APJCP.2014.15.15.6315
  2. Evaluation of HER-2/neu Overexpression in Gastric Carcinoma using a Tissue Microarray vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7597
  3. Clinicopathological Significance of CD133 and ALDH1 Cancer Stem Cell Marker Expression in Invasive Ductal Breast Carcinoma vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7491
  4. Emerging Roles of Krüppel-Like Factor 4 in Cancer and Cancer Stem Cells vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3629
  5. Distinct prognostic values of ALDH1 isoenzymes in breast cancer vol.36, pp.4, 2015, https://doi.org/10.1007/s13277-014-2852-6
  6. RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells vol.6, pp.5, 2015, https://doi.org/10.1038/cddis.2015.128
  7. Cancer stem cell research in Iran: potentials and challenges vol.13, pp.20, 2017, https://doi.org/10.2217/fon-2017-0091
  8. Role of ALDH1a and CD44 in transitional and squamous cell carcinomas of urinary bladder vol.37, pp.1, 2017, https://doi.org/10.1097/01.XEJ.0000516729.34502.81
  9. CD133 and CD44 as cancer stem cell markers in bladder carcinoma vol.37, pp.1, 2017, https://doi.org/10.1097/01.XEJ.0000520912.41715.09
  10. Exploration of bladder cancer molecular mechanisms based on miRNA-mRNA regulatory network vol.37, pp.3, 2017, https://doi.org/10.3892/or.2017.5433
  11. Curcumin reversed chronic tobacco smoke exposure induced urocystic EMT and acquisition of cancer stem cells properties via Wnt/β-catenin vol.8, pp.10, 2017, https://doi.org/10.1038/cddis.2017.452
  12. Renal cell carcinoma with synchronous ipsilateral urothelial carcinoma of the renal pelvis vol.13, pp.6, 2017, https://doi.org/10.3892/ol.2017.5981
  13. The promise of stem cell markers in the diagnosis and therapy of epithelial dysplasia and oral squamous cell carcinoma vol.233, pp.11, 2018, https://doi.org/10.1002/jcp.26789