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http://dx.doi.org/10.14348/molcells.2019.2280

Radiation-Induced CXCL12 Upregulation via Histone Modification at the Promoter in the Tumor Microenvironment of Hepatocellular Carcinoma  

Ahn, Hak Jun (Department of Life Science, College of Natural Sciences,)
Hwang, Soon Young (Department of Life Science, College of Natural Sciences,)
Nguyen, Ngoc Hoan (Department of Life Science, College of Natural Sciences,)
Lee, Ik Jae (Department of Radiation Oncology, Yonsei University Medical College, Yonsei University Health System)
Lee, Eun Jeong (Department of Radiation Oncology, Yonsei University Medical College, Yonsei University Health System)
Seong, Jinsil (Department of Radiation Oncology, Yonsei University Medical College, Yonsei University Health System)
Lee, Jong-Soo (Department of Life Science, College of Natural Sciences,)
Publication Information
Molecules and Cells / v.42, no.7, 2019 , pp. 530-545 More about this Journal
Abstract
Tumor cells can vary epigenetically during ionizing irradiation (IR) treatment. These epigenetic variegations can influence IR response and shape tumor aggressiveness. However, epigenetic disturbance of histones after IR, implicating in IR responsiveness, has been elusive. Here, we investigate whether altered histone modification after IR can influence radiation responsiveness. The oncogenic CXCL12 mRNA and protein were more highly expressed in residual cancer cells from a hepatoma heterotopic murine tumor microenvironment and coculture of human hepatoma Huh7 and normal IMR90 cells after radiation. H3K4 methylation was also enriched and H3K9 methylation was decreased at its promoter region. Accordingly, invasiveness and the subpopulation of aggressive $CD133^+/CD24^-$ cells increased after IR. Histone demethylase inhibitor IOX1 attenuated CXCL12 expression and the malignant subpopulation, suggesting that responses to IR can be partially mediated via histone modifications. Taken together, radiation-induced histone alterations at the CXCL12 promoter in hepatoma cells are linked to CXCL12 upregulation and increased aggressiveness in the tumor microenvironment.
Keywords
CXCL12; histone modification; malignancy; radiation; tumor microenvironment;
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1 Sun, X., Zhang, T., Deng, Q., Zhou, Q., Sun, X., Li, E., Yu, D., and Zhong, C. (2018). Benzidine induces epithelial-mesenchymal transition of human bladder cancer cells through activation of ERK5 pathway. Mol. Cells 41, 188-197.   DOI
2 Teicher, B.A. and Fricker, S.P. (2010). CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin. Cancer Res. 16, 2927-2931.   DOI
3 Trautmann, F., Cojoc, M., Kurth, I., Melin, N., Bouchez, L.C., Dubrovska, A., and Peitzsch, C. (2014). CXCR4 as biomarker for radioresistant cancer stem cells. Int. J. Radiat. Biol. 90, 687-699.   DOI
4 Uy, G.L., Rettig, M.P., Motabi, I.H., McFarland, K., Trinkaus, K.M., Hladnik, L.M., Kulkarni, S., Abboud, C.N., Cashen, A.F., Stockerl-Goldstein, K.E., et al. (2012). A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood 119, 3917-3924.   DOI
5 Wurth, R., Bajetto, A., Harrison, J.K., Barbieri, F., and Florio, T. (2014). CXCL12 modulation of CXCR4 and CXCR7 activity in human glioblastoma stem-like cells and regulation of the tumor microenvironment. Front. Cell. Neurosci. 8, 144.   DOI
6 Zahnow, C.A. (2011). CCAAT/enhancer-binding protein ${\beta}$: its role in breast cancer and associations with receptor tyrosine kinases. Expert Rev. Mol. Med. 11, e12.   DOI
7 Dobrynin, G., McAllister, T.E., Leszczynska, K.B., Ramachandran, S., Krieg, A.J., Kawamura, A., and Hammond, E.M. (2017). KDM4A regulates HIF-1 levels through H3K9me3. Sci. Rep. 11, 11094.
8 Domanska, U.M., Kruizinga, R.C., Nagengast, W.B., Timmer-Bosscha, H., Huls, G., de Vries, E.G., and Walenkamp, A.M. (2013). A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur. J. Cancer 49, 219-230.   DOI
9 Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Binger, D.D., and Rich, J.N. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756-760.   DOI
10 Ahuja, N., Easwaran, H., and Baylin, S.B. (2014). Harnessing the potential of epigenetic therapy to target solid tumors. J. Clin. Invest. 124, 56-63.   DOI
11 Chatterjee, S., Behnam Azad, B., and Nimmagadda, S. (2014). The intricate role of CXCR4 in cancer. Adv. Cancer Res. 124, 31-82.   DOI
12 Choi, J.D. and Lee, J.S. (2013). Interplay between epigenetics and genetics in cancer. Genomics Inform. 11, 164-173.   DOI
13 Hong, S.W., Hur, W., Choi, J.E., Kim, J.H., Hwang, D., and Yoon, S.K. (2016). Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation. Oncotarget 7, 23482-23497.   DOI
14 Dubrovska, A., Elliott, J., Salamone, R.J., Telegeev, G.D., Stakhovsky, A.E., Schepotin, I.B., Yan, F., Wang, Y., Bouchez, L.C., Kularatne, S.A., et al. (2012). CXCR4 expression in prostate cancer progenitor cells. PLoS One 7, e31226.   DOI
15 Eke, I. and Cordes, N. (2011). Radiobiology goes 3D: how ECM and cell morphology impact on cell survival after irradiation. Radiother. Oncol. 99, 271-278.   DOI
16 Fu, S.L., Pang, H., Xu, J.Z., and Wu, X.H. (2014). $C/EBP{\beta}$ mediates osteoclast recruitment by regulating endothelial progenitor cell expression of SDF-$1{\alpha}$. PLoS One 9, e91217.   DOI
17 Guillot, C., Favaudon, V., Herceg, Z., Sagne, C., Sauvaigo, S., Merle, P., and Chemin, I. (2014). PARP inhibition and the radiosensitizing effects of the PARP inhibitor ABT-888 in in vitro hepatocellular carcinoma models. BMC Cancer 14, 603.   DOI
18 Haubner, F., Ohmann, E., Pohl, F., Struts, J., and Gassner, H.G. (2012). Wound healing after radiation therapy: review of the literature. Radiat. Oncol. 7, 162.   DOI
19 Hu, Q., Chen, J., Zhang, J., Xu, C., Yang, S., and Jiang, H. (2015). IOX1, a JMJD2A inhibitor, suppresses the proliferation and migration of vascular smooth muscle cells induced by angiotensin II by regulating the expression of cell cycle-related proteins. Int. J. Mol. Med. 37, 189-196.   DOI
20 Imaizumi, N., Monnier, Y., Hegi, M., Mirimanoff, R.O., and Ruegg, C. (2010). Radiotherapy suppresses angiogenesis in mice through TGF-${\beta}$RI/ALK5-dependent inhibition of endothelial cell sprouting. PLos One 5, e11084.   DOI
21 Kuonen, F., Secondini, C., and Ruegg, C. (2012). Molecular pathways: emerging pathways mediating growth, invasion, and metastasis of tumors progressing in an irradiated microenvironment. Clin. Cancer Res. 18, 5196-5202.   DOI
22 Jung, M.J., Rho, J.K., Kim, Y.M., Jung, J.E., Jin, Y.B., Ko, Y.G., Lee, J.S., Lee, S.J., Lee, J.C., and Park, M.J. (2013). Upregulation of CXCR4 is functionally crucial for maintenance of stemness in drug-resistant non-small cell lung cancer cells. Oncogene 32, 209-221.   DOI
23 Junttila, M.R. and Sauvage, F.J. (2013). Influence of tumor microenvironment heterogeneity on therapeutic response. Nature 501, 346-354.   DOI
24 Kong, F.M., Cuneo, K.C., Wang, L., Bonner, J.A., Gaspar, L.E., Komaki, R., Sun, A., Morris, D.E., Sandler, H.M., and Movas, B. (2014). Patterns of practice in radiation therapy for non-small cell lung cancer among members of the American Society for Radiation Oncology. Pract. Radiat. Oncol. 4, e133-e141.   DOI
25 Krause, M., Yaromina, A., Eicheler, W., Koch, U., and Baumann, M. (2011). Cancer stem cells: targets and potential biomarkers for radiotherapy. Clin. Cancer Res. 17, 7224-7229.   DOI
26 Kryczek, I., Wei, S., Keller, E., Liu, R., and Zou, W. (2007). Stromal derived factor (SDF-1/CXCL12) and human tumor pathogenesis. Am. J. Physiol. Cell Physiol. 292, C987-C995.   DOI
27 Lagadec, C., Vlashi, E., Della Donna, L., Dekmezian, C., and Pajonk, F. (2012). Radiation-induced reprogramming of breast cancer cells. Stem Cells 30, 833-844.   DOI
28 Lee, I.J., Lee, E.J., Park, H., Kim, W., Ha, S.J., Shin, Y.K., and Seong, J. (2016). Altered biological potential and radioresponse of murine tumors in different microenvironments. Cancer Res. Treat. 48, 727-737.   DOI
29 Rich, J.N. (2007). Cancer stem cells in radiation resistance. Cancer Res. 67, 8980-8984.   DOI
30 Lumniczky, K. and Sáfrány, G. (2015). The impact of radiation therapy on the antitumor immunity: local effects and systemic consequences. Cancer Lett. 356, 114-125.   DOI
31 Romain, B., Benbrika-Nehmar, R., Marisa, L., Legrain, M., Lobstein, V., Oravecz, A., Poidevin, L., Bour, C., Freund, J.N., Duluc, I., et al. (2017). Histone hypoacetylation contributes to CXCL12 downregulation in colon cancer: impact of tumor and cell migration. Oncotarget 8, 38351-38366.   DOI