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Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays
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 Title & Authors
Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays
Salim, Elsayed I; Hegazi, Mona M; Kang, Jin Seok; Helmy, Hager M;
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 Abstract
The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemically-induced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.
 Keywords
Colon cancer;rat;cancer stem cells;flow cytometry;ALDH1;EpCAM;CD44;CD133;PCNA;
 Language
English
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 References
1.
Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A, 100, 3983-8. crossref(new window)

2.
Al-Henhena N, Khalifa SA, Ying RP, et al (2015). Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo. BMC Complement Altern Med, 15, 419. crossref(new window)

3.
Aruffo A, Stamenkovic I, Melnick M, et al (1990). CD44 is the principal cell surface receptor for hyaluronate. Cell, 61, 1303-13. crossref(new window)

4.
Barker N, Ridgway RA, van Es JH, et al (2009). Crypt stem cells as the cells of origin of intestinal cancer. Nature, 457, 608-12. crossref(new window)

5.
Basiji DA, Ortyn WE, Liang L, Venkatachalam V, Morrissey P (2007). Cellular image analysis and imaging by flow cytometry. Clin Lab Med, 27, 653-70. crossref(new window)

6.
Boman BM, Walters R, Fields JZ, et al (2004). Colonic crypt changes during adenoma development in familial adenomatous polyposis: immunohistochemical evidence for expansion of the crypt base cell population. Am J Pathol, 165, 1489-98. crossref(new window)

7.
Boman BM, Fields JZ, Cavanaugh KL, et al (2008a). How dysregulated colonic crypt dynamics cause stem cell overpopulation and initiate colon cancer. Cancer Res, 6, 3304-13.

8.
Boman BM, Huang E (2008b). Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. J Clin Oncol, 26, 2828-38. crossref(new window)

9.
Bonnet D (2005). Cancer stem cells. AMLs show the way. Biochem Soc Trans, 33, 1531-3. crossref(new window)

10.
Cheng C, Sharp PA (2006). Regulation of CD44 alternative splicing by SRm160 and its potential role in tumor cell invasion. Mol Cell Biol, 26, 362-70. crossref(new window)

11.
Corpet DE, Tache S (2002). Most effective colon cancer chemopreventive agents in rats: A systematic review of aberrant crypt foci and tumor data, ranked by potency. Nutr Cancer, 43, 1-21. crossref(new window)

12.
Costabile V, Duraturo F, Delrio P et al (2015). Lithium chloride induces mesenchymal to epithelial reverting transition in primary colon cancer cell cultures. Int J Oncol, 46, 1913-23. crossref(new window)

13.
Dalerba P, Dylla SJ, Park IK, et al (2007). Phenotypic characterization of human colorectal cancer stem cells. PNAS, 104, 10158-163. crossref(new window)

14.
Dean PN, Jett JH (1974). Mathematical analysis of DNA distributions derived from microfluorometry. J Cell Biol, 40, 523-7.

15.
Dylla SJ, Beviglia L, Park IK, et al (2008). Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS ONE, 3, 2428. crossref(new window)

16.
Elzagheid A, Algars A, Bendardaf R, et al (2006). E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. World J Gastroenterol, 12, 4304-9. crossref(new window)

17.
Fearon ER, Vogelstein B (1990). A genetic model for colorectal tumorigenesis. Cell, 61, 759-67. crossref(new window)

18.
Fernandes CR, Turatti A, Gouvea DR, et al (2011). The protective role of Lychnophora ericoides Mart. (Brazilian arnica) in 1,2-dimethylhydrazine-induced experimental colon carcinogenesis. Nutr Cancer, 63, 593-9. crossref(new window)

19.
Fhu CW, Graham AM, Yap CT, et al (2014). Reed-Sternberg cell-derived lymphotoxin-${\alpha}$ activates endothelial cells to enhance T-cell recruitment in classical Hodgkin lymphoma. Blood, 124, 2973-82. crossref(new window)

20.
Hsu SM, Raine L, Fanger H, (1981). Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem. Cytochem, 29, 577-580. crossref(new window)

21.
Huang EH, Hynes MJ, Zhang T, et al (2009). Aldehyde Dehydrogenase 1 is a marker for normal and malignant human colonic stem cells and tracks stem cell overpopulation during colon tumorigenesis. Cancer Res, 69, 3382-9. crossref(new window)

22.
Kim JY, Alam F, Chung SW (2014). Combinational chemoprevention effect of Celecoxib and an oral antiangiogenic LHD4 on colorectal carcinogenesis in mice. Anticancer Drugs, 25, 1061-71. crossref(new window)

23.
Kochi T, Shimizu M, Shirakami Y, et al (2015). Utility of Apcmutant rats with a colitis-associated colon carcinogenesis model for chemoprevention studies. Eur J Cancer Prev, 24, 180-7. crossref(new window)

24.
Kopp R, Fichter M, Schalhorn G, Danescu J, Classen S (2009). Frequent expression of the high molecular, 673-bp CD44v3, v8-10 variant in colorectal adenomas and carcinomas. Int J Mol Med, 24, 677-83.

25.
Kuniyasu H, Ohmori H, Sasaki T (2003). Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis. Clin Cancer Res, 9, 4802-10.

26.
Lei Du, Hongyi Wang, Leya He, et al (2008). CD44 is of functional importance for colorectal cancer stem cells. Clin Cancer Res, 6751.

27.
Levi E, Mohammad R, Kodali U (2004). EGF-receptor related protein causes cell cycle arrest and induces apoptosis of colon cancer cells in vitro and in vivo. Anticancer Res, 24(5A), 2885-91.

28.
Liu R, Shen Y, Nan K, et al (2015). Association Between Expression Of Cancer Stem Cell Markers And Poor Differentiation Of Hepatocellular Carcinoma: A Meta-Analysis (Prisma). Med (Baltimore), 94, 1306. crossref(new window)

29.
Losi L, Roncucci L, Digregorio C, et al (1996). K-ras and P53 mutation in human colorectal aberrant crypt foci. J Pathol, 128, 259-63.

30.
Lynch PM, Burke CA, Phillips R, et al (2015). An international randomised trial of Celecoxib versus Celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis. Gut, 307235.

31.
Malmstrom PU, Busch C, Norlen BJ, et al (1988). Expression of ABH blood group isoantigen as a prognostic factor in transitional cell bladder carcinoma. Scand J Urol Nephrol, 22, 265-70. crossref(new window)

32.
Marcato P, Dean CA, Giacomantonio CA, Lee PW (2011). Aldehyde dehydrogenase: its role as a cancer stem cell marker comes down to the specific isoform. Cell Cycle, 10, 1378-84 crossref(new window)

33.
Munz M, Baeuerle PA, Gires O (2009). The emerging role of epcam in cancer and stem cell signaling. Cancer Res, 69, 5627-9. crossref(new window)

34.
Nautiyal J, Du J, Yu Y, (2012). EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine. Am J Physiol Gastrointest Liver Physiol, 302, 655-63. crossref(new window)

35.
O’Brien CA, Pollett A, Gallinger S, Dick JE (2007). A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 445, 106-10. crossref(new window)

36.
O'Leary KE, Cruess DG, Pleau D, et al (2011). Sex differences in associations between psychosocial factors and aberrant crypt foci among patients at risk for colon cancer. Gend Med, 8, 165-71 crossref(new window)

37.
Osta WA, Chen Y, Mikhitarian K (2004). EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res, 64, 5818-24. crossref(new window)

38.
Ottinger S, Kloppel A, Rausch V, Liu L, Kallifatidis G, Gross W, Gebhard MM, Brummer F, Herr I (2012). Targeting of pancreatic and prostate cancer stem cell characteristics by Crambe crambe marine sponge extract. Int J Cancer, 130, 1671-81. crossref(new window)

39.
Parafiniewicz B, Pendzich J, Gruchlik A (2012). Impact of celecoxib on soluble intercellular adhesion molecule-1 and soluble E-Cadherin concentrations in human colon cancer cell line cultures exposed to phytic acid and TNF-${\alpha}$. Acta Poloniae Pharmaceutica Drug Res, 69, 1283-90.

40.
Patlolla JM, Zhang Y, Li Q, et al (2012). Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. Int J Oncol, 40, 170-5.

41.
Patriarca C, Macchi RM, Marschner AK, et al (2012). E-cadherin expression pattern in primary colorectal carcinomas and their metastases reflects disease outcome. Cancer Treat Rev, 38, 68-75. crossref(new window)

42.
Pommergaard HC, Burcharth J, Rosenberg J, et al (2015). Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial. Gastroenterol, 6-5085(15)01354-2.

43.
Rao CV, Steele VE, Swamy MV, (2009). Inhibition of azoxymethane-induced colorectal cancer by CP-31398, a TP53 modulator, alone or in combination with low doses of celecoxib in male F344 rats. Cancer Res, 69, 8175-82. crossref(new window)

44.
Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, et al (2007). Identification and expansion of human coloncancer-initiating cells. Nature, 445, 111-5. crossref(new window)

45.
Roncucci L, Medline A, Bruce WR (1991). Classification of aberrant crypt foci and microadenomas in human colon. Cancer Epidemiol Biomarkers Prev, 1, 57-60.

46.
Saini MK, Sanyal SN (2012). PTEN regulates apoptotic cell death through PI3-K/Akt/$GSK3{\beta}$ signaling pathway in DMH induced early colon carcinogenesis in rat. Exp Mol Pathol, 93, 135-46. crossref(new window)

47.
Santisteban M, Reiman JM, Asiedu MK, et al, (2009). Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res, 69, 2887-95. crossref(new window)

48.
Shen J, Wanibuchi H, Salim EI, et al (2003). Induction of glutathione S-transferase placental form-positive foci in liver and epithelial hyperplasia in urinary bladder, but no tumor development in male Fischer 344 rats treated with monomethylarsonic acid for 104 weeks. Toxicol and Applied Pharmacol, 193, 335-45. crossref(new window)

49.
Skidan I, Steiniger SC. (2014). In vivo models for cancer stem cell research: a practical guide for frequently used animal models and available biomarkers. J Physiol Pharmacol, 65, 157-69.

50.
Steinbach G, Lynch PM, Phillips RK, et al (2000). The effect of celecoxib,a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med, 342, 1946-52. crossref(new window)

51.
Tagde A, Singh H, Kang MH, Reynolds CP (2014). The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma. Blood Cancer J, 4, 229. crossref(new window)

52.
Tang ZC, Shivapurkar N, Frost A, et al (1996). The effect of dietary fat on the promotion of mammary and colon cancer in a dual organ rat carcinogenesis model. Nutr Cancer, 25, 151-9. crossref(new window)

53.
Traganos F, Darzynkiewicz Z, Sharpless T, et al (1977). Simultaneous staining of ribonucleic and deoxyribonucleic acids in unfixed cells using acridine orange in a flow cytofluorometric system. J Histochem Cytochem, 25, 46-56. crossref(new window)

54.
van der Gun BT, Melchers LJ, Ruiters MH, et al (2010). EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis, 11, 1913-21.

55.
Tutlewska K, Lubinski J, Kurzawski G (2013). Hered. Germline deletions in the EPCAM gene as a cause of Lynch syndrome - literature review. Cancer Clin Pract, 11, 9. crossref(new window)

56.
van de Wetering M, Sancho E, Verweij C, et al (2002). The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell, 111, 241-50. crossref(new window)

57.
Wang L, Chen F, Zhang Z, Chen G, Luo J, Shi X (2012). Cancer stem cells in the mechanism of metal carcinogenesis. J Environ Pathol Toxicol Oncol, 31, 245-63. crossref(new window)

58.
Went PT, Lugli A, Meier S (2004). Frequent EpCam protein expression in human carcinomas. Hum Pathol, 35, 122-8. crossref(new window)

59.
Yamamoto H, Imai K (2015). Microsatellite instability: an update, Arch Toxicol, 89, 899-921. crossref(new window)

60.
Zhu L, Gibson P, Currle DS, et al (2009). Prominin 1 marks intestinal stem cells that are susceptible to neoplastictransformation. Nature, 457, 603-8. crossref(new window)