Therapeutic potential of human adipose stem cells in a cancer stem cell-like gastric cancer cell model

Liu,Guangming; Neumeister,Michael; Reichensperger,Joel; Yang,Russell   D.

doi:10.3892/ijo.2013.2039

Therapeutic potential of human adipose stem cells in a cancer stem cell-like gastric cancer cell model

Authors:
- Guangming Liu
- Michael Neumeister
- Joel Reichensperger
- Russell D. Yang
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Affiliations: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL 62794, USA, Department of Plastic Surgery, Southern Illinois University School of Medicine, Springfield, IL 62794, USA
Published online on: July 25, 2013 https://doi.org/10.3892/ijo.2013.2039
Pages: 1301-1309

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Abstract

Cancer stem cells (CSCs) or circulating tumor cells play an important role in tumor initiation, invasion, metastasis and resistance to anticancer therapies. Therapies that target gastric tumor CSCs have potential clinical application for preventing malignant gastric tumor progression and metastasis. We isolated CD44+ gastric cancer cells from the gastric cancer cell line AGS and Hs746T cells and maintained the cells in a novel stem cell culture. The cells were kept in an undifferentiated proliferative state and we characterized their cancer stem cell properties and chemotherapy-resistance behavior. The CD44+ cancer cells were also co-cultured with human adipose stem cells (ADSCs) to determine the chemotherapy-promotion effects of the adipose cells on the CD44+ cancer cells. The CD44+ gastric cancer cell model is a non-adhesion, 3-dimensional, spheroid phenotype. The non-adherent CD44+ cells have cancer stem cell properties and are highly chemo-resistant. However, these cells regained chemo-sensitivity when re-attached to an extracellular matrix-coated attachment surface. The human adipose stem cells significantly promoted the chemo-sensitivity of the non-adherent CD44+ gastric cancer cells. Integrin α2/β2 and the Wnt signaling pathways are involved in the mechanisms. We concluded that the in vitro non-adherent CD44+ gastric cancer cell model resembles the circulating gastric tumor cells in vivo. Introduction of an appropriate attachment surface significantly promotes chemo-sensitivity of the non-adherent CD44+ gastric cancer cells. The human adipose stem cells function as a ‘living vehicle surface’ for such a purpose in vivo.

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1.	Raimondi C, Naso G, Gradilone A, Gianni W, Cortesi E and Gazzaniga P: Circulating tumor cells in cancer therapy: are we off target? Curr Cancer Drug Targets. 10:509–518. 2010. View Article : Google Scholar : PubMed/NCBI
2.	Takaishi S, Okumura T, Tu S, et al: Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 27:1006–1020. 2009. View Article : Google Scholar : PubMed/NCBI
3.	Mayer B, Klement G, Kaneko M, Man S, Jothy S, Rak J and Kerbel RS: Multicellular gastric cancer spheroids recapitulate growth pattern and differentiation phenotype of human gastric carcinomas. Gastroenterology. 121:839–852. 2001. View Article : Google Scholar
4.	O’Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007.PubMed/NCBI
5.	Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle 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
6.	Boman BM and Huang E: Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. J Clin Oncol. 26:2828–2838. 2008. View Article : Google Scholar : PubMed/NCBI
7.	Han ME, Jeon TY, Hwang SH, et al: Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci. 68:3589–3605. 2011. View Article : Google Scholar : PubMed/NCBI
8.	Vilalta M, Dégano IR, Bagó J, Aguilar E, Gambhir SS, Rubio N and Blanco J: Human adipose tissue derived mesenchymal stromal cells as vehicles for tumor bystander effect: a model based on bioluminescence imaging. Gene Ther. 16:547–557. 2009. View Article : Google Scholar
9.	Lamfersd M, Idema S, van Milligen F, et al: Homing properties of adipose-derived stem cells to intracerebral glioma and the effects of adenovirus infection. Cancer Lett. 274:78–87. 2009. View Article : Google Scholar : PubMed/NCBI
10.	Iyengar P, Combs TP, Shah SJ, et al: Adipocyte-secreted factors synergistically promote mammary tumorigenesis through induction of anti-apoptotic transcriptional programs and protooncogene stabilization. Oncogene. 22:6408–6423. 2003. View Article : Google Scholar
11.	Manabe Y, Toda S, Miyazaki K and Sugihara H: Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. J Pathol. 201:221–228. 2003. View Article : Google Scholar : PubMed/NCBI
12.	Muehlberg FL, Song YH, Krohn A, et al: Tissue-resident stem cells promote breast cancer growth and metastasis. Carcinogenesis. 30:589–597. 2009. View Article : Google Scholar : PubMed/NCBI
13.	Sun B, Roh KH, Park JR, et al: Therapeutic potential of mesenchymal stromal cells in a mouse breast cancer metastasis model. Cytotherapy. 11:289–298. 2009. View Article : Google Scholar : PubMed/NCBI
14.	Casteilla L, Planat-Benard V, Laharrague P and Cousin B: Adipose-derived stromal cells: their identity and uses in clinical trials, an update. World J Stem Cells. 3:25–33. 2011. View Article : Google Scholar : PubMed/NCBI
15.	Chakrabarty S, Wang H, Canaff L, Hendy GN, Appelman H and Varani J: Calcium sensing receptor in human colon carcinoma: interaction with Ca(2+) and 1,25-dihydroxyvitamin D(3). Cancer Res. 65:493–498. 2005.PubMed/NCBI
16.	Chakrabarty S, Radjendirane V, Appelman H and Varani J: Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E-cadherin expression and suppression of beta-catenin/TCF activation. Cancer Res. 63:67–71. 2003.
17.	Zajickova K, Vrbikova J, Canaff L, Pawelek PD, Goltzman D and Hendy GN: Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status. J Clin Endocrinol Metab. 92:2616–2623. 2007. View Article : Google Scholar
18.	Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM and McEwan RN: A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 47:3239–3245. 1987.PubMed/NCBI
19.	Liu G, Bode A, Ma WY, Sang S, Ho CT and Dong Z: Two novel glycosides from the fruits of Morinda citrifolia (noni) inhibit AP-1 transactivation and cell transformation in the mouse epidermal JB6 cell line. Cancer Res. 61:5749–5756. 2001.PubMed/NCBI
20.	Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW and Zoeller M: CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med. 8:784–804. 2008. View Article : Google Scholar : PubMed/NCBI
21.	Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S and Smith A: Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell. 113:643–655. 2003. View Article : Google Scholar : PubMed/NCBI
22.	Fukuda S and Pelus LM: Survivin, a cancer target with an emerging role in normal adult tissues. Mol Cancer Ther. 5:1087–1098. 2006. View Article : Google Scholar : PubMed/NCBI
23.	Zaffaroni N and Daidone MG: Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions. Drug Resist Updat. 5:65–72. 2002. View Article : Google Scholar : PubMed/NCBI
24.	Marsh S: Thymidylate synthase pharmacogenetics. Invest New Drugs. 23:533–537. 2005. View Article : Google Scholar
25.	Rose MG, Farrell MP and Schmitz JC: Thymidylate synthase: a critical target for cancer chemotherapy. Clin Colorectal Cancer. 1:220–229. 2002. View Article : Google Scholar : PubMed/NCBI
26.	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI
27.	Li X, Lewis MT, Huang J, et al: Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 100:672–679. 2008. View Article : Google Scholar : PubMed/NCBI
28.	Vermeulen L, Todaro M, de Sousa Mello F, et al: Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA. 105:13427–13432. 2008. View Article : Google Scholar : PubMed/NCBI
29.	Odoux C, Fohrer H, Hoppo T, et al: A stochastic model for cancer stem cell origin in metastatic colon cancer. Cancer Res. 68:6932–6941. 2008. View Article : Google Scholar : PubMed/NCBI
30.	Cousin B, Ravet E, Poglio S, et al: Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo. PLoS One. 4:e62782009. View Article : Google Scholar : PubMed/NCBI
31.	Grisendi G, Bussolari R, Cafarelli L, et al: Adipose-derived mesenchymal stem cells as stable source of tumor necrosis factor-related apoptosis-inducing ligand delivery for cancer therapy. Cancer Res. 70:3718–3729. 2010.
32.	Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA and Lander ES: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 138:645–659. 2009. View Article : Google Scholar : PubMed/NCBI