Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 9/2016

01-09-2016 | Original Article

Primary cultures of human colon cancer as a model to study cancer stem cells

Authors: Sergey Koshkin, Anna Danilova, Grigory Raskin, Nikolai Petrov, Olga Bajenova, Stephen J. O’Brien, Alexey Tomilin, Elena Tolkunova

Published in: Tumor Biology | Issue 9/2016

Login to get access

Abstract

The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient’s tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.
Literature
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 66(1):7–30.
2.
Chang GJ, CY H, Eng C, Skibber JM, Rodriguez-Bigas MA. Practical application of a calculator for conditional survival in colon cancer. J Clin Oncol. 2009;27:5938–43.CrossRefPubMed
3.
Ishida H, Fujita K, Akiyama Y, Sunakawa Y, Yamashita K, Mizuno K, et al. Regimen selection for first-line FOLFIRI and FOLFOX based on UGT1A1 genotype and physical background is feasible in Japanese patients with advanced colorectal cancer. Jpn J Clin Oncol. 2011;41:617–23.CrossRefPubMed
4.
Sanli UA, Karabulut B, Uslu R, Korkut M, Goker E. Single-agent irinotecan for recurrent/metastatic colorectal cancer: a retrospective analysis. Med Princ Pract. 2006;15:288–92.CrossRefPubMed
5.
Valent P, Bonnet D, De Maria R, Lapidot T, Copland M, Melo JV, et al. Cancer stem cell definitions and terminology: the devil is in the details. Nat Rev Cancer. 2012;12:767–75.CrossRefPubMed
6.
Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–8.CrossRefPubMed
7.
Ricci-Vitiani L, Fabrizi E, Palio E, De Maria R. Colon cancer stem cells. J Mol Med (Berl). 2009;87:1097–104.CrossRef
8.
Fabian A, Barok M, Vereb G, Szollosi J. Die hard: are cancer stem cells the Bruce Willises of tumor biology? Cytometry A. 2009;75:67–74.CrossRefPubMed
9.
Vaiopoulos AG, Kostakis ID, Koutsilieris M, Papavassiliou AG. Colorectal cancer stem cells. Stem Cells. 2012;30:363–71.CrossRefPubMed
10.
Mathonnet M, Perraud A, Christou N, Akil H, Melin C, Denizot Y, et al. Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells. World J Gastroenterol. 2014;20:4189–96.CrossRefPubMedPubMedCentral
11.
O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106–10.CrossRefPubMed
12.
Van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A, van der Horn K, Clevers H. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002;111:241–50.CrossRefPubMed
13.
XS W, Xi HQ, Chen L. Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival. World J Surg Oncol. 2012;10:244.14.
14.
Ritsma L, Ellenbroek SI, Zomer A, Snippert HJ, de Sauvage FJ, van Rheenen J, et al. Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature. 2014;507:362–5.CrossRefPubMedPubMedCentral
15.
Gargett CE, Schwab KE, Zillwood RM, Nguyen HP, Wu D. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009;80:1136–45.CrossRefPubMedPubMedCentral
16.
Ebben JD, Treisman DM, Zorniak M, Kutty RG, Clark PA, Kuo JS. The cancer stem cell paradigm: a new understanding of tumor development and treatment. Expert Opin Ther Targets. 2010;14:621–32.CrossRefPubMedPubMedCentral
17.
CS Y, Huang AC, Lai KC, Huang YP, Lin MW, Chung JG, et al. Diallyltrisulfide induces apoptosis in human primary colorectal cancer cells. Oncol Rep. 2012;28:94954.
18.
Todaro M, Orlando V, Cicero G, Caccamo N, Meraviglia S, Dieli F, et al. Chemotherapy sensitizes colon cancer initiating cells to Vy9V52 T cell-mediated cytotoxicity. PLoS One. 2013;8.
19.
Khan IN, Al-Karim S, Bora RS, Chaudhary AG, Saini KS. Cancer stem cells: a challenging paradigm for designing targeted drug therapies. Drug Discov Today. 2015;20(10):1205–16.CrossRefPubMed
20.
Tomayko MM, Reynolds CP, Euhus DM, Hudd C, LaRegina MC, Johnson FE. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol. 1989;24(3):148–54.CrossRefPubMed
21.
Liskovykh MA, Chuikin IA, Ranjan A, Safina DA, Tolkunova EN, Tomilin AN, et al. Generation of rat induced pluripotent stem cells: the analysis of reprogramming and culturing media. Tsitologiia. 2011;53:939–45.PubMed
22.
Davydov-Sinitsyn AP, Bazhenova OV, Liskovykh MA, Ponomartsev CV, Tomilin AN, Tolkunova EN, et al. In vitro derivation and characterization of a colorectal cancer stem cell subpopulation. Tsitologiia. 2013;55:318–23.PubMed
23.
Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Petrelli NJ, et al. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J ClinOncol. 1993;11:187987.
24.
Cunningham D, Pyrhonen S, James RD, Punt CJ, Hickish TF, Herait P, et al. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998;352:1413–8.CrossRefPubMed
25.
Hochedlinger K, Yamada Y, Beard C, Jaenisch R. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell. 2005;121:465–77.CrossRefPubMed
26.
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Jemal A. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64:252–71.CrossRefPubMed
27.
Siegel R, DeSantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64:104–17.CrossRefPubMed
28.
29.
Kaddis N, Saif MW. Second-line treatment for pancreatic cancer. JOP. 2014;15:344347.
30.
Tanase CP, Neagu AI, Necula LG, Mambet C, Enciu AM, Albulescu R, et al. Cancer stem cells: involvement in pancreatic cancer pathogenesis and perspectives on cancer therapeutics. World J Gastroenterol. 2014;20:10790–801.CrossRefPubMedPubMedCentral
31.
Muqbil I, Bao GW, El-Kharraj R, Shah M, Mohammad RM, Azmi AS et al. Systems and network pharmacology approaches to cancer stem cells research and therapy. J Stem Cell Res Ther. 2012;suppl 7.
32.
Wang YJ, Herlyn M. The emerging roles of Oct4 in tumor-initiating cells. Am J Phys Cell Phys. 2015;309(11):C709–18.
33.
Poursani EM, Mohammad Soltani B, Mowla SJ. Differential expression of OCT4 pseudogenes in pluripotent and tumor cell lines. Cell J. 2016;18(1):28–36.PubMedPubMedCentral
34.
Kobayashi I, Takahashi F, Nurwidya F, Nara T, Hashimoto M, Takahashi K. Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells. Biochem Biophys Res Commun. 2016;473(1):125–32.CrossRefPubMed
35.
Fazlul H. Sarkar. Novel holistic approaches for overcoming therapy resistance in pancreatic and colon cancers. Med Princ Pract 2015.
36.
37.
Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeu-len L, Stassi G. Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell. 2007;1:389–402.CrossRefPubMed
38.
Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, Ellis LM, et al. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009;69:1951–7.CrossRefPubMedPubMedCentral
39.
Dieter SM, Ball CR, Hoffmann CM, Nowrouzi A, Herbst F, Glimm H, et al. Distinct types of tumor-initiating cells form human colon cancer tumors and metastases. Cell Stem Cell. 2011;9:357–65.CrossRefPubMed
40.
41.
Pitynski K, Banas T, Pietrus M, Milian-Ciesielska K, Ludwin A, Okon K. SOX-2, but not Oct4, is highly expressed in early-stage endometrial adenocarcinoma and is related to tumour grading. Int J Clin Exp Pathol. 2015;8:8189–98.PubMedPubMedCentral
42.
Ji J, Wei X, Wang Y. Embryonic stem cell markers Sox-2 and OCT4 expression and their correlation with WNT signal pathway in cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2014;7:2470–86.PubMedPubMedCentral
43.
Yang F, Gao Y, Geng J, Qu D, Han Q, Chen G, et al. Elevated expression of SOX2 and FGFR1 in correlation with poor prognosis in patients with small cell lung cancer. Int J Clin Exp Pathol. 2013;6:2846–54.PubMedPubMedCentral
44.
Wang Q, He W, Lu C, Wang Z, Wang J, Suo Z, et al. Oct3/4 and Sox2 are significantly associated with an unfavorable clinical outcome in human esophageal squamous cell carcinoma. Anticancer Res. 2009;29:1233–41.PubMed
45.
Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa, Kusunoki M, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16:3488–98.CrossRefPubMed
46.
Hosokawa Y, Takahashi H, Inoue A, Kawabe Y, Funahashi Y, Tanaka J, et al. Oct-3/4 modulates the drug- resistant phenotype of glioblastoma cells through expression of ATP binding cassette transporter G2. Biochim Biophys Acta. 2015;1850:1197–205.CrossRefPubMed
47.
Kashihara H, Shimada M, Kurita N, Iwata T, Sato H, Matsumoto N, et al. CD133 expression is correlated with poor prognosis in colorectal cancer. Hepato-Gastroenterology. 2014;61:1563–7.PubMed
48.
Vicente-Duenas C, Gutierrez de Diego J, Rodriguez FD, Jimenez R, Cobaleda C. The role of cellular plasticity in cancer development. Curr Med Chem. 2009;16:3676–85.CrossRefPubMed
49.
50.
Deng YH, XX P, Huang MJ, Xiao J, Zhou JM, Lin EH, et al. 5-Fluorouracil upregulates the activity of Wnt signaling pathway in CD133-positive colon cancer stemlike cells. Chin J Cancer. 2010;29:810–5.CrossRefPubMed
51.
Qi L, Sun B, Liu Z, Li H, Gao J, Leng X. Dickkopf-1 inhibits epithelial-mesenchymal transition of colon cancer cells and contributes to colon cancer suppression. Cancer Sci. 2012;103:828–35.CrossRefPubMed
52.
Fan F, Bellister S, Lu J, Ye X, Boulbes DR, Ellis LM, et al. The requirement for freshly isolated human colorectal cancer (CRC) cells in isolating CRC stem cells. Br J Cancer. 2015;112:539–46.CrossRefPubMed
53.
Barker N, Clevers H. Leucine-rich repeat-containing G-protein-coupled receptors as markers of adult stem cells. Gastroenterology. 2010;138:1681–96.CrossRefPubMed
54.
Metadata
Title
Primary cultures of human colon cancer as a model to study cancer stem cells
Authors
Sergey Koshkin
Anna Danilova
Grigory Raskin
Nikolai Petrov
Olga Bajenova
Stephen J. O’Brien
Alexey Tomilin
Elena Tolkunova
Publication date
01-09-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5214-8

Other articles of this Issue 9/2016

Tumor Biology 9/2016 Go to the issue

Original Article

The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy

Review

Multiple roles of CD90 in cancer

Original Article

Integrinβ1 modulates tumour resistance to gemcitabine and serves as an independent prognostic factor in pancreatic adenocarcinomas

Original Article

A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease

Commentary

Note of the methodological flaws in the paper entitled “GSTT1 and GSTM1 polymorphisms predict treatment outcome for breast cancer: a systematic review and meta-analysis”

Original Article

The value of plasma netrin-1 in non-small cell lung cancer patients as diagnostic and prognostic biomarker
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits