Stem cell models for genetically predisposed colon cancer (Review)

Telang,Nitin

doi:10.3892/ol.2020.11998

Stem cell models for genetically predisposed colon cancer (Review)

Authors:
- Nitin Telang
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Affiliations: Cancer Prevention Research Program, Palindrome Liaisons Consultants, Montvale, NJ 07645‑1559, USA
Published online on: August 20, 2020 https://doi.org/10.3892/ol.2020.11998
Article Number: 138

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Abstract

Negative growth regulatory tumor suppressor genes and positive growth regulatory oncogenes serve important roles in initiation/progression of colon cancer. Germline mutation in the adenomatous polyposis coli (APC) tumor suppressor gene represents a primary genetic defect for familial adenomatous polyposis (FAP) syndrome, a predisposing factor for clinical colon cancer. Somatic mutations in the APC gene are common in sporadic colon cancer. Preclinical and clinical efficacy is documented for targeted therapy with non‑steroidal anti‑inflammatory drugs, selective cyclo‑oxygenase‑2 inhibitors for prostaglandin biosynthesis and selective inhibitor of ornithine decarboxylase for polyamine biosynthesis. However, these therapeutic options lead to systemic toxicity, acquired tumor resistance and emergence of therapy resistant cancer stem cells. By contrast, non‑toxic natural products are unlikely to exhibit drug resistance and may represent testable alternatives for therapy resistant colon cancer. Tumorigenic Apc [‑/‑] colonic epithelial cell lines derived from preclinical FAP models provide novel cellular models for drug resistant cancer stem cells. Apc [‑/‑] Sulindac resistant (SUL‑R) cells exhibit upregulated expression levels of cancer stem cell markers. Natural products, such as naturally occurring vitamin A derivative all‑trans retinoic acid (ATRA) and the anti‑cancer agent from Turmeric root curcumin (CUR), represent testable alternatives. Relative to the non‑tumorigenic Apc [+/+] C57 COL colonic epithelial cells, the tumorigenic Apc [‑/‑] 1638N COL and Apc [‑/‑] ⁸⁵⁰ MIN COL cells exhibit aneuploid cell hyper‑proliferation and upregulated expression of Apc target genes β‑catenin, cyclin D1, c‑myc and COX‑2. The SUL‑R phenotypes exhibit enhanced tumor spheroid formation and upregulated expression levels of stem cell markers CD44, CD133 and c‑Myc. Treatment of the SUL‑R stem cells with ATRA and CUR inhibits tumor spheroid formation and reduces the expression of stem cell markers. Stem cell models developed for FAP syndrome provide a novel experimental approach to identify mechanistic leads for efficacious natural products as testable alternatives for therapy‑resistant, genetically predisposed colon cancer.

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1	Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell. 61:759–767. 1990. View Article : Google Scholar : PubMed/NCBI
2	Fodde R, Smits R and Clevers H: APC, signal transduction and genetic instability in colon cancer. Nat Rev Cancer. 1:55–67. 2001. View Article : Google Scholar : PubMed/NCBI
3	Levine AJ, Jenkins NA and Copeland NG: The roles of initiating truncal mutations in human cancers: The order of mutations and tumor cell type matters. Cancer Cell. 35:10–15. 2019. View Article : Google Scholar : PubMed/NCBI
4	Fodde R, Edelman W, Yang K, Van Leuwen C, Carlson C, Renault B, Breukel C, Alt E, Lipkin M, Khan PM, et al: A targeted chain termination mutation in the mouse Apc gene results in multiple intestinal tumors. Proc Natl Acad Sci USA. 91:8969–8973. 1994. View Article : Google Scholar : PubMed/NCBI
5	Su LK, Kinzler KW, Vogelstein B, Preisinger AC, Moser AR, Luongo C, Gould KA and Dove WF: Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene. Science. 256:668–670. 1992. View Article : Google Scholar : PubMed/NCBI
6	Beazer-Barclay Y, Levy DB, Moser AR, Dove WF, Hamilton SR, Vogelstein B and Kinzler KW: Sulindac suppresses tumorigenesis in in the min mouse. Carcinogenesis. 17:1757–1760. 1996. View Article : Google Scholar : PubMed/NCBI
7	Jacoby RF, Seibert K, Cole CE, Kelloff G and Lubet RA: The cyclooxygenase-2 inhibitor celecoxib is a potent preventive and therapeutic agent in the min mouse model of adenomatous polyposis. Cancer Res. 60:5040–5044. 2000.PubMed/NCBI
8	Boolbol SK, Dannenberg AL, Chadburn A, Martucci C, Guo XJ, Ramonetti JT, Abreu-Goris M, Newmark HL, Lipkin ML, DeCosse JJ and Bertagnolli MM: Cyclooxygenase-2 overexpression and tumor formation are blocked by sulindac in a murine model of familial adenomatous polyposis. Cancer Res. 56:2556–2560. 1996.PubMed/NCBI
9	Ju J, Hong J, Zhou JN, Pan Z, Bose M, Liao J, Yang GY, Liu YY, Hou Z, Lin Y, et al: Inhibition of intestinal tumorigenesis in Apcmin/+ mice by (−)-epigallocatechin-3-gallate, the major catechin in green tea. Cancer Res. 65:10623–10631. 2005. View Article : Google Scholar : PubMed/NCBI
10	Perkins S, Verschoyle RD, Hill K, Parveen I, Threadgil MD, Sharma RA, Williams ML, Steward WP and Gescher AJ: Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epid Biomark Prev. 11:535–540. 2002.
11	Giardiello FM, Hamilton SR, Krush AJ, Piantadisis S, Hylind LM, Cellano P, Brooker SV, Robinson CR and Offerhans GL: Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 328:1313–1316. 1993. View Article : Google Scholar : PubMed/NCBI
12	Steinbeck G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, et al: The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 342:1946–1952. 2000. View Article : Google Scholar : PubMed/NCBI
13	Gupta RA and Dubois RN: Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 1:11–21. 2001. View Article : Google Scholar : PubMed/NCBI
14	JacobyR F, Cole CE, Tutsch F, Newton MA, Kelloff G, Hawk ET and Lubet RA: Chemopreventive efficacy of combined piroxicam and difluoromethylornithine treatment of Apc mutant min mouse adenomas, and selective toxicity against Apc mutant embryos. Cancer Res. 60:1864–1870. 2000.PubMed/NCBI
15	Swamy MV, Patlolla JMR, Steele VE, Kopelovich L, Reddy BS and Rao CV: Chemoprevention of familial adenomatous polyposis by low doses of atorvastatin and celecoxib given individually and in combination to APCMin mice. Cancer Res. 66:7370–7377. 2006. View Article : Google Scholar : PubMed/NCBI
16	Meyskens FL Jr, McLaren CE, Pelot D, Fujikawa-Brooks S, Carpenter PM, Hawk E, Kelloff G, Lawson MJ, Kidao J, McCracken J, et al: Difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas: A randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila). 1:32–38. 2008. View Article : Google Scholar : PubMed/NCBI
17	Dean M, Fojo T and Bates S: Tumor stem cells and drug resistance. Nat Rev Cancer. 5:275–284. 2005. View Article : Google Scholar : PubMed/NCBI
18	Telang NT, Li G and Katdare M: Prevention of early-onset familial/hereditary colon cancer: New models and mechanistic biomarkers (review). Int J Oncol. 28:1523–1529. 2006.PubMed/NCBI
19	Telang N and Katdare M: Combinatorial prevention of carcinogenic risk in a model for familial colon cancer. Oncol Rep. 17:909–914. 2007.PubMed/NCBI
20	Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, Tamaki Y and Noguchi S: 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. 15:4234–4241. 2009. View Article : Google Scholar : PubMed/NCBI
21	Van Phuc P, Nhan PL, Nhung TH, Tam NT, Hoang NM, Tue VG, Thuy DT and Ngoc PK: Downregulation of CD44 reduces doxorubicin resistance of CD44CD24 breast cancer cells. Onco Targets Ther. 4:71–78. 2011. View Article : Google Scholar : PubMed/NCBI
22	Zhang F, Song C, Ma Y, Tang L, Xu Y and Wang H: Effect of fibroblasts on breast cancer cell mammosphere formation and regulation of stem cell-related gene expression. Int J Mol Med. 28:365–371. 2011.PubMed/NCBI
23	Dalebra P, Dylla SJ, Park IK, Luiu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simone DM, et al: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 104:10158–10163. 2007. View Article : Google Scholar : PubMed/NCBI
24	O'Brien CA, Polett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007. View Article : Google Scholar : PubMed/NCBI
25	Ricci-Vitiani L, Lombardi DG, Pillozi E, Biffoni M, Todaro M, Peschele C and De Maria R: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
26	Crespo M, Villar E, Tsai SY, Chang K, Amin S, Srinivasan T, Zhang T, Pipalia NH, Chen HJ, Witherspoon M, et al: Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med. 23:878–884. 2017. View Article : Google Scholar : PubMed/NCBI
27	Takahashi K, Tanabe K, Ohnuli M, Narita M, Ishsaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar : PubMed/NCBI
28	Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW and Daley GQ: Reprogramming of human somatic cells to pluripotency with defined factors. Nature. 451:141–146. 2008. View Article : Google Scholar : PubMed/NCBI
29	Yu J, Hu K, Smuga-Otto K, Tian S, Stuart R, Slukvin II and Thompson JA: Human induced pluripotent stem cells free of vector and transgene sequences. Science. 324:797–801. 2009. View Article : Google Scholar : PubMed/NCBI
30	Telang N: Anti-inflammatory drug resistance selects putative cancer stem cells in a cellular model for genetically predisposed colon cancer. Oncol Letts. 15:642–648. 2018.
31	Katdare M, Kopelovich L and Telang N: Efficacy of chemopreventive agents for growth inhibition of Apc [+/−] 1638NCOL colonic epithelial cells. Int J Mol Med. 10:427–432. 2002.PubMed/NCBI
32	Telang N and Katdare M: Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome. Oncol Rep. 21:1017–1021. 2009. View Article : Google Scholar : PubMed/NCBI
33	Telang NT and Williams GM: Carcinogen-induced DNA damage and cellular alterations in F344 rat colon organ cultures. J Natl Cancer Inst. 68:1015–1022. 1982.PubMed/NCBI
34	Anastas JN and Moon RT: WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 13:11–26. 2013. View Article : Google Scholar : PubMed/NCBI
35	Wang C, Xie CJ, Guo J, Manning HC, Gore JC and Gou N: Evaluation of CD44 and CD133 as cancer stem cell markers for colorectal cancer. Oncol Rep. 28:1301–1308. 2012. View Article : Google Scholar : PubMed/NCBI
36	Zhou JY, Chen M, Ma I, Wang X, Chen YG and Lui SL: Role of CD44(high)/CD133(high) HCT-116 cells in the tumorigenesis of colon cancer. Oncotarget. 7:7657–7666. 2016. View Article : Google Scholar : PubMed/NCBI
37	Zeilstra J, Joosten SP, Dokter M, Verwiel E, Spaargaren M and Pals ST: Deletion of the WNT target and cancer stem cell marker CD44 in Apc(Min/+) mice attenuates intestinal tumorigenesis. Cancer Res. 68:3655–3661. 2008. View Article : Google Scholar : PubMed/NCBI
38	Moser AR, Pitot HC and Dove WF: A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science. 247:322–324. 1990. View Article : Google Scholar : PubMed/NCBI
39	Sinicrope FA, Velamala PR, Song LMWK, Viggiano TR, Bruining DH, Rajan E, Gostout CJ, Kraichely RE, Buttar NS, Schroeder KW, et al: Efficacy of difluoromethylornithine and aspirin for treatment of adenomas and aberrant crypt foci in patients with prior advanced colorectal neoplasms. Cancer Prev Res (Phila). 12:821–830. 2019. View Article : Google Scholar : PubMed/NCBI
40	Zhou W, Kallifaditis G, Baumann B, Rausch V, Mattern J, Galdkich J, Geiss N, Moldenhaur G, Wirth T, Büchler MW, et al: Dietary polyphenol quercetin targets pancreatic cancer stem cells. Int J Oncol. 37:551–561. 2010.PubMed/NCBI
41	Rausch V, Liu I, Kallifatidis G, Baumann B, Mattern J, Gladkich I, Wirth T, Schemmer P, Buchler MW, Zöller M, et al: Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer Res. 70:5004–5013. 2010. View Article : Google Scholar : PubMed/NCBI
42	Kallifatidis G, Labsch S, Rausch V, Mattern J, Gladkich J, Moldenhauer G, Büchler MW, Salnikov AV and Herr I: Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol Ther. 19:188–195. 2011. View Article : Google Scholar : PubMed/NCBI
43	Nguyen PH, Giraud J, Staedel C, Chambonnier L, Dubus P, Chevret E, Bœuf H, Gautherea X, Rousseau B, Fevre M, et al: All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. Oncogene. 35:5619–5628. 2016. View Article : Google Scholar : PubMed/NCBI
44	Castro NP, Rangel MC, Merchant AS, MacKnnon G, Cuttitta F, Salomon DA and Kim YS: Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo. Cancer Prev Res (Phila). 12:147–158. 2019. View Article : Google Scholar : PubMed/NCBI
45	Kim SH and Singh SV: Role of Krüppel-like factor 4-p21^CIP1 axis in breast cancer stem-like cell inhibition by benzyl isothiocyanate. Cancer Prev Res (Phila). 12:125–134. 2019. View Article : Google Scholar : PubMed/NCBI
46	Telang N: Stem cell targeted therapeutic approaches for molecular subtypes of clinical breast cancer (Review). World Acad Sci J. 1:20–24. 2019. View Article : Google Scholar
47	Telang N: Targeting drug resistance stem cells in a human epidermal growth factor receptor-2-enriched breast cancer model. World Acad Sci J. 1:86–91. 2019.
48	Matano M, date S, Shimokava M, Takano A, Fuji M, Ohta Y, Watanabe T, Konai T and Sato M: Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med. 21:256–262. 2015. View Article : Google Scholar : PubMed/NCBI
49	Li Y, Li X, Qu J, Luo D and Hu Z: Cas9 mediated correction of β-catenin mutation and restoring the expression of protein phosphorylation in colon cancer HCT-116 cells decrease cell proliferation in vitro and hamper tumor growth in mice in vivo. Onco Targets Ther. 13:17–29. 2020. View Article : Google Scholar : PubMed/NCBI
50	Drost J, van Jaarsveld RH, Ponsioen B, Zimberlin C, van Boxtel R, Buijs A, Sachs N, Overmeer RM, Offerhaus GJ, Begthel H, et al: Sequential cancer mutations in cultured human intestinal stem cells. Nature. 521:43–47. 2015. View Article : Google Scholar : PubMed/NCBI