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http://dx.doi.org/10.14348/molcells.2017.0089

CD133 Regulates IL-1β Signaling and Neutrophil Recruitment in Glioblastoma  

Lee, Seon Yong (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Kim, Jun-Kyum (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Jeon, Hee-Young (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Ham, Seok Won (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Kim, Hyunggee (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Publication Information
Molecules and Cells / v.40, no.7, 2017 , pp. 515-522 More about this Journal
Abstract
CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.
Keywords
CD133; glioblastoma; IL-$1{\beta}$ signaling; neutrophil; U87MG glioma cell;
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1 Brat, D.J., Castellano-Sanchez, A.A., Hunter, S.B., Pecot, M., Cohen, C., Hammond, E.H., Devi, S.N., Kaur, B., and Van Meir, E.G. (2004). Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population. Cancer Res. 64, 920-927.   DOI
2 Brescia, P., Richichi, C., and Pelicci, G. (2012). Current strategies for identification of glioma stem cells: adequate or unsatisfactory? J. Oncol. 2012, 376894.
3 Zeppernick, F., Ahmadi, R., Campos, B., Dictus, C., Helmke, B.M., Becker, N., Lichter, P., Unterberg, A., Radlwimmer, B., Herold-Mende, C.C., et al. (2008). Stem cell marker CD133 affects clinical outcome in glioma patients. Clin. Cancer Res. 14, 123-129.   DOI
4 Zhang, L., Zhang, L., Li, H., Ge, C., Zhao, F., Tian, H., Chen, T., Jiang, G., Xie, H., Cui, Y., et al. (2016). CXCL3 contributes to CD133(+) CSCs maintenance and forms a positive feedback regulation loop with CD133 in HCC via Erk1/2 phosphorylation. Sci. Rep. 6, 27426.   DOI
5 Zhu, L., Finkelstein, D., Gao, C., Shi, L., Wang, Y., Lopez-Terrada, D., Wang, K., Utley, S., Pounds, S., Neale, G., et al. (2016). Multi-organ mapping of cancer risk. Cell 166, 1132-1146.   DOI
6 Zahreddine, H., and Borden, K.L. (2013). Mechanisms and insights into drug resistance in cancer. Front. Pharmacol. 4, 28.
7 Eramo, A., Ricci-Vitiani, L., Zeuner, A., Pallini, R., Lotti, F., Sette, G., Pilozzi, E., Larocca, L.M., Peschle, C., and De Maria, R. (2006). Chemotherapy resistance of glioblastoma stem cells. Cell Death Differ. 13, 1238-1241.   DOI
8 Brescia, P., Ortensi, B., Fornasari, L., Levi, D., Broggi, G., and Pelicci, G. (2013). CD133 is essential for glioblastoma stem cell maintenance. Stem Cells 31, 857-869.   DOI
9 Chen, K., Huang, Y.H. and Chen, J.L. (2013). Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta. Pharmacol. Sin. 34, 732-740.   DOI
10 Eash, K.J., Greenbaum, A.M., Gopalan, P.K., and Link, D.C. (2010). CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J. Clin. Invest. 120, 2423-2431.   DOI
11 Griguer, C.E., Oliva, C.R., Gobin, E., Marcorelles, P., Benos, D.J., Lancaster, J.R. Jr., and Gillespie, G.Y. (2008). CD133 is a marker of bioenergetic stress in human glioma. PloS One 3, e3655.   DOI
12 Han, M., Guo, L., Zhang, Y., Huang, B., Chen, A., Chen, W., Liu, X., Sun, S., Wang, K., Liu, A., et al. (2016). Clinicopathological and prognostic significance of CD133 in glioma patients: A meta-analysis. Mol. Neurobiol. 53, 720-727.   DOI
13 Highfill, S.L., Cui, Y., Giles, A.J., Smith, J.P., Zhang, H., Morse, E., Kaplan, R.N., and Mackall, C.L. (2014). Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci. Transl. Med. 6, 237ra67.   DOI
14 Kaiser, J. (2015). The cancer stem cell gamble. Science 347, 226-229.   DOI
15 Klonisch, T., Wiechec, E., Hombach-Klonisch, S., Ande, S.R., Wesselborg, S., Schulze-Osthoff, K., and Los, M. (2008). Cancer stem cell markers in common cancers - therapeutic implications. Trends Mol. Medicine 14, 450-460.   DOI
16 Pearson, M.J., Philp, A.M., Heward, J.A., Roux, B.T., Walsh, D.A., Davis, E.T., Lindsay, M.A., and Jones, S.W. (2016). Long intergenic noncoding RNAs mediate the human chondrocyte inflammatory response and are differentially expressed in osteoarthritis cartilage. Arthritis Rheumatol. 68, 845-856.
17 Lathia, J.D., Mack, S.C., Mulkearns-Hubert, E.E., Valentim, C.L., and Rich, J.N. (2015). Cancer stem cells in glioblastoma. Genes Dev. 29, 1203-1217.   DOI
18 Omuro, A., and DeAngelis, L.M. (2013). Glioblastoma and other malignant gliomas: a clinical review. JAMA 310, 1842-1850.   DOI
19 Pallini, R., Ricci-Vitiani, L., Montano, N., Mollinari, C., Biffoni, M., Cenci, T., Pierconti, F., Martini, M., De Maria, R., and Larocca, L.M. (2011). Expression of the stem cell marker CD133 in recurrent glioblastoma and its value for prognosis. Cancer 117, 162-174.   DOI
20 Park, E.K., Lee, J.C., Park, J.W., Bang, S.Y., Yi, S.A., Kim, B.K., Park, J.H., Kwon, S.H., You, J.S., Nam, S.W., et al. (2015). Transcriptional repression of cancer stem cell marker CD133 by tumor suppressor p53. Cell Death Dis. 6, e1964.   DOI
21 Rempel, S.A., Dudas, S., Ge, S., and Gutierrez, J.A. (2000). Identification and localization of the cytokine SDF1 and its receptor, CXC chemokine receptor 4, to regions of necrosis and angiogenesis in human glioblastoma. Clin. Cancer Res. 6, 102-111.
22 Sharma, V., Dixit, D., Ghosh, S., and Sen, E. (2011a). COX-2 regulates the proliferation of glioma stem like cells. Neurochem. Int. 59, 567-571.   DOI
23 Sharma, V., Dixit, D., Koul, N., Mehta, V.S., and Sen, E. (2011b). Ras regulates interleukin-1beta-induced HIF-1alpha transcriptional activity in glioblastoma. J. Mol. Med. 89, 123-136.   DOI
24 Wei, Y., Jiang, Y., Zou, F., Liu, Y., Wang, S., Xu, N., Xu, W., Cui, C., Xing, Y., Liu, Y., et al. (2013). Activation of PI3K/Akt pathway by CD133-p85 interaction promotes tumorigenic capacity of glioma stem cells. Proc. Natl. Acad. Sci. USA 110, 6829-6834.   DOI
25 Soeda, A., Park, M., Lee, D., Mintz, A., Androutsellis-Theotokis, A., McKay, R.D., Engh, J., Iwama, T., Kunisada, T., Kassam, A.B., et al. (2009). Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene 28, 3949-3959.   DOI
26 Steele, C.W., Karim, S.A., Leach, J.D., Bailey, P., Upstill-Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., et al. (2016). CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma. Cancer Cell 29, 832-845.   DOI
27 Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., et al. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545-15550.   DOI
28 Sunkin, S.M., Ng, L., Lau, C., Dolbeare, T., Gilbert, T.L., Thompson, C.L., Hawrylycz, M., and Dang, C. (2013). Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 41, D996-D1008.
29 Wang, G., Lu, X., Dey, P., Deng, P., Wu, C.C., Jiang, S., Fang, Z., Zhao, K., Konaparthi, R., Hua, S., et al. (2016). Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov. 6, 80-95.   DOI
30 Wu, Y. and Wu, P.Y. (2009). CD133 as a marker for cancer stem cells: progresses and concerns. Stem Cells Dev. 18, 1127-1134.   DOI
31 Yeung, Y.T., McDonald, K.L., Grewal, T., and Munoz, L. (2013). Interleukins in glioblastoma pathophysiology: implications for therapy. Br. J. Pharmacol. 168, 591-606.   DOI