DOI QR코드

DOI QR Code

Sox12 Is a Cancer Stem-Like Cell Marker in Hepatocellular Carcinoma

  • Zou, Song (Department of Interventional Oncology, the People's Hospital of Ganzhou) ;
  • Wang, Chen (Department of Oncology, the People's Hospital of Ganzhou) ;
  • Liu, Jiansheng (Department of Oncology, the People's Hospital of Ganzhou) ;
  • Wang, Qun (Department of Oncology, the Affiliated Hospital of Guilin Medical University) ;
  • Zhang, Dongdong (Department of Oncology, the Affiliated Hospital of Guilin Medical University) ;
  • Zhu, Shengnan (Department of Oncology, the Affiliated Hospital of Guilin Medical University) ;
  • Xu, Shengyuan (Department of Oncology, the Affiliated Hospital of Guilin Medical University) ;
  • Kang, Mafei (Department of Oncology, the Affiliated Hospital of Guilin Medical University) ;
  • He, Shaozhong (Department of Oncology, the Affiliated Hospital of Guilin Medical University)
  • Received : 2017.07.07
  • Accepted : 2017.08.25
  • Published : 2017.11.30

Abstract

Recent studies on molecular carcinogenesis suggest that the chemo-resistance of some cancers is largely due to presence of cancer stem cells (CSCs), which affect the chemotherapy outcome for hepatocellular carcinoma (HCC). However, currently no consensus on a CSC phenotype in HCC has been obtained. Here, we examined Sox12 as a novel CSC marker in HCC. Sox12+ versus Sox12- cells were purified from HCC cell lines. The Sox12+ cells were compared with Sox12- HCC cells for tumor sphere formation, chemo-resistance, tumor formation after serial adoptive transplantations in nude mice, and the frequency of developing distal metastasis. We found that compared to Sox12- HCC cells, Sox12+ HCC cells generated significantly more tumor spheres in culture, were more chemo-resistant to cisplatin, were detected in circulation more frequently, and formed distal tumor more frequently. Moreover, Sox12 appeared to functionally contribute to the stemness of HCC cells. Thus, we conclude that Sox12 may be a novel marker for enriching CSCs in HCC.

Keywords

References

  1. Armstrong, L., Stojkovic, M., Dimmick, I., Ahmad, S., Stojkovic, P., Hole, N., and Lako, M. (2004). Phenotypic characterization of murine primitive hematopoietic progenitor cells isolated on basis of aldehyde dehydrogenase activity. Stem Cells 22, 1142-1151. https://doi.org/10.1634/stemcells.2004-0170
  2. Brower, V. (2016). Sorafenib plus cisplatin for hepatocellular carcinoma. Lancet Oncol 17, e424. https://doi.org/10.1016/S1470-2045(16)30447-8
  3. Chiba, T., Iwama, A. and Yokosuka, O. (2016). Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology. Hepatol Res 46, 50-57. https://doi.org/10.1111/hepr.12548
  4. Cockrell, A.S., and Kafri, T. (2007). Gene delivery by lentivirus vectors. Mol. Biotechnol. 36, 184-204. https://doi.org/10.1007/s12033-007-0010-8
  5. Duester, G. (2000). Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur. J. Biochem. 267, 4315-4324. https://doi.org/10.1046/j.1432-1327.2000.01497.x
  6. Dy, P., Penzo-Mendez, A., Wang, H., Pedraza, C.E., Macklin, W.B., and Lefebvre, V. (2008) The three SoxC proteins--Sox4, Sox11 and Sox12--exhibit overlapping expression patterns and molecular properties. Nucleic Acids Res 36, 3101-3117. https://doi.org/10.1093/nar/gkn162
  7. Fang, D.D., Kim, Y.J., Lee, C.N., Aggarwal, S., McKinnon, K., Mesmer, D., Norton, J., Birse, C.E., He, T., Ruben, S.M., et al. (2010). Expansion of CD133(+) colon cancer cultures retaining stem cell properties to enable cancer stem cell target discovery. Br. J. Cancer 102, 1265-1275. https://doi.org/10.1038/sj.bjc.6605610
  8. Hess, D.A., Meyerrose, T.E., Wirthlin, L., Craft, T.P., Herrbrich, P.E., Creer, M.H., and Nolta, J.A. (2004). Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood 104, 1648-1655. https://doi.org/10.1182/blood-2004-02-0448
  9. Hess, D.A., Wirthlin, L., Craft, T.P., Herrbrich, P.E., Hohm, S.A., Lahey, R., Eades, W.C., Creer, M.H., and Nolta, J.A. (2006). Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood 107, 2162-2169. https://doi.org/10.1182/blood-2005-06-2284
  10. Hess, D.A., Craft, T.P., Wirthlin, L., Hohm, S., Zhou, P., Eades, W.C., Creer, M.H., Sands, M.S., and Nolta, J.A. (2008). Widespread nonhematopoietic tissue distribution by transplanted human progenitor cells with high aldehyde dehydrogenase activity. Stem Cells 26, 611-620. https://doi.org/10.1634/stemcells.2007-0429
  11. Hoser, M., Potzner, M.R., Koch, J.M., Bosl, M.R., Wegner, M., and Sock, E. (2008). Sox12 deletion in the mouse reveals nonreciprocal redundancy with the related Sox4 and Sox11 transcription factors. Mol. Cell Biol. 28, 4675-4687. https://doi.org/10.1128/MCB.00338-08
  12. Houghton, B.C., Booth, C., and Thrasher, A.J. (2015). Lentivirus technologies for modulation of the immune system. Curr. Opin. Pharmacol. 24, 119-127. https://doi.org/10.1016/j.coph.2015.08.007
  13. Huang, R., and Rofstad, E.K. (2017). Cancer stem cells (CSCs), cervical CSCs and targeted therapies. Oncotarget 8, 35351-35367.
  14. Huang, W., Chen, Z., Shang, X., Tian, D., Wang, D., Wu, K., Fan, D., and Xia, L. (2015). Sox12, a direct target of FoxQ1, promotes hepatocellular carcinoma metastasis through up-regulating Twist1 and FGFBP1. Hepatology 61, 1920-1933. https://doi.org/10.1002/hep.27756
  15. Ikeda, M., Shimizu, S., Sato, T., Morimoto, M., Kojima, Y., Inaba, Y., Hagihara, A., Kudo, M., Nakamori, S., Kaneko, S., et al. (2016). Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial. Ann. Oncol. 27, 2090-2096. https://doi.org/10.1093/annonc/mdw323
  16. Iqbal, W., Alkarim, S., AlHejin, A., Mukhtar, H., and Saini, K.S. (2016). Targeting signal transduction pathways of cancer stem cells for therapeutic opportunities of metastasis. Oncotarget 7, 76337-76353.
  17. Jiang, T., Guan, L.Y., Ye, Y.S., Liu, H.Y., and Li, R. (2017). MiR-874 inhibits metastasis and epithelial-mesenchymal transition in hepatocellular carcinoma by targeting SOX12. Am. J. Cancer Res. 7, 1310-1321.
  18. Llovet, J.M., and Bruix, J. (2008). Novel advancements in the management of hepatocellular carcinoma in 2008. J. Hepatol. 48 Suppl 1, S20-37.
  19. Ma, I., and Allan, A.L. (2011). The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 7, 292-306. https://doi.org/10.1007/s12015-010-9208-4
  20. Ma, S., Chan, K.W., Lee, T.K., Tang, K.H., Wo, J.Y., Zheng, B.J., and Guan, X.Y. (2008). Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res 6, 1146-1153. https://doi.org/10.1158/1541-7786.MCR-08-0035
  21. Magni, M., Shammah, S., Schiro, R., Mellado, W., Dalla-Favera, R., and Gianni, A.M. (1996). Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood 87, 1097-1103.
  22. Matsuo, N., Shiraha, H., Fujikawa, T., Takaoka, N., Ueda, N., Tanaka, S., Nishina, S., Nakanishi, Y., Uemura, M., Takaki, A., et al. (2009). Twist expression promotes migration and invasion in hepatocellular carcinoma. BMC Cancer 9, 240. https://doi.org/10.1186/1471-2407-9-240
  23. McCarron, A., Donnelley, M., McIntyre, C., and Parsons, D. (2016). Challenges of up-scaling lentivirus production and processing. J. Biotechnol. 240, 23-30. https://doi.org/10.1016/j.jbiotec.2016.10.016
  24. Nagata, T., Sakakura, C., Komiyama, S., Miyashita, A., Nishio, M., Murayama, Y., Komatsu, S., Shiozaki, A., Kuriu, Y., Ikoma, H., et al. (2011). Expression of cancer stem cell markers CD133 and CD44 in locoregional recurrence of rectal cancer. Anticancer Res. 31, 495-500.
  25. Nakata, S., Phillips, E., and Goidts, V. (2014). Emerging role for leucine-rich repeat-containing G-protein-coupled receptors LGR5 and LGR4 in cancer stem cells. Cancer Manag. Res. 6, 171-180.
  26. Ottaiano, A. (2010). Finding markers for cancer stem cells in renal cell carcinoma: looking beyond CD133. Cell Cycle 9, 4431. https://doi.org/10.4161/cc.9.22.13823
  27. Perez-Losada, J., and Balmain, A. (2003) Stem-cell hierarchy in skin cancer. Nat. Rev. Cancer 3, 434-443. https://doi.org/10.1038/nrc1095
  28. Petersson, M. and Niemann, C. (2012) Stem cell dynamics and heterogeneity: implications for epidermal regeneration and skin cancer. Curr. Med. Chem. 19, 5984-5992. https://doi.org/10.2174/0929867311209065984
  29. Ray, P.E., Al-Attar, A., Liu, X.H., Das, J.R., Tassi, E. and Wellstein, A. (2014) Expression of a Secreted Fibroblast Growth Factor Binding Protein-1 (FGFBP1) in Angioproliferative Kaposi Sarcoma. J. AIDS Clin. Res. 5.
  30. Shi, C., Tian, R., Wang, M., Wang, X., Jiang, J., Zhang, Z., Li, X., He, Z., Gong, W., and Qin, R. (2010) CD44+ CD133+ population exhibits cancer stem cell-like characteristics in human gallbladder carcinoma. Cancer Biol. Ther. 10, 1182-1190. https://doi.org/10.4161/cbt.10.11.13664
  31. Silva, I.A., Bai, S., McLean, K., Yang, K., Griffith, K., Thomas, D., Ginestier, C., Johnston, C., Kueck, A., Reynolds, R.K., et al. (2011) Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res. 71, 3991-4001. https://doi.org/10.1158/0008-5472.CAN-10-3175
  32. Singh, S.R. (2012). Stem cell niche in tissue homeostasis, aging and cancer. Curr. Med. Chem. 19, 5965-5974. https://doi.org/10.2174/0929867311209065965
  33. Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003). Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821-5828.
  34. Sun, B., Zhang, D., Zhao, N., and Zhao, X. (2017). Epithelial-to-endothelial transition and cancer stem cells: two cornerstones of vasculogenic mimicry in malignant tumors. Oncotarget 8, 30502-30510.
  35. Verslype, C., Van Cutsem, E., Dicato, M., Arber, N., Berlin, J.D., Cunningham, D., De Gramont, A., Diaz-Rubio, E., Ducreux, M., Gruenberger, T., et al. (2009). The management of hepatocellular carcinoma. Current expert opinion and recommendations derived from the 10th World Congress on Gastrointestinal Cancer, Barcelona, 2008. Ann. Oncol. 20 Suppl 7, vii1-vii6.
  36. Yan, Y., Zuo, X. and Wei, D. (2015). Concise review: emerging Role of CD44 in cancer stem cells: a promising biomarker and therapeutic target. Stem Cells Transl. Med. 4, 1033-1043. https://doi.org/10.5966/sctm.2015-0048
  37. Yang, M.H., Chen, C.L., Chau, G.Y., Chiou, S.H., Su, C.W., Chou, T.Y., Peng, W.L., and Wu, J.C. (2009). Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology 50, 1464-1474. https://doi.org/10.1002/hep.23221
  38. Yang, Z., Yang, Z., Zou, Q., Yuan, Y., Li, J., Li, D., Liang, L., Zeng, G., and Chen, S. (2014). A comparative study of clinicopathological significance, FGFBP1, and WISP-2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of the gallbladder. Int. J. Clin. Oncol. 19, 325-335. https://doi.org/10.1007/s10147-013-0550-9
  39. Zhang, H., and Li, S.Y. (2010). Research progression of CD133 as a marker of cancer stem cells. Chinese J. Cancer 29, 243-247. https://doi.org/10.5732/cjc.009.10587
  40. Zhang, C.H., Xu, G.L., Jia, W.D., Li, J.S., Ma, J.L., Ren, W.H., Ge, Y.S., Yu, J.H., Liu, W.B., and Wang, W. (2012). Activation of STAT3 signal pathway correlates with twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance. J. Surg. Res. 174, 120-129. https://doi.org/10.1016/j.jss.2010.10.030
  41. Zhang, C., Guo, F., Xu, G., Ma, J., and Shao, F. (2015). STAT3 cooperates with Twist to mediate epithelial-mesenchymal transition in human hepatocellular carcinoma cells. Oncol. Rep. 33, 1872-1882. https://doi.org/10.3892/or.2015.3783
  42. Zhu, H.Y., Bai, W.D., Liu, J.Q., Zheng, Z., Guan, H., Zhou, Q., Su, L.L., Xie, S.T., Wang, Y.C., Li, J., et al. (2016) Up-regulation of FGFBP1 signaling contributes to miR-146a-induced angiogenesis in human umbilical vein endothelial cells. Sci. Rep. 6, 25272. https://doi.org/10.1038/srep25272

Cited by

  1. Spindle pole body component 25 regulates stemness of prostate cancer cells vol.10, pp.11, 2017, https://doi.org/10.18632/aging.101631
  2. SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis vol.10, pp.3, 2017, https://doi.org/10.1038/s41419-019-1481-9
  3. Human Hepatic Cancer Stem Cells (HCSCs) Markers Correlated With Immune Infiltrates Reveal Prognostic Significance of Hepatocellular Carcinoma vol.11, pp.None, 2017, https://doi.org/10.3389/fgene.2020.00112
  4. Recent Advances in Liver Cancer Stem Cells: Non-coding RNAs, Oncogenes and Oncoproteins vol.8, pp.None, 2017, https://doi.org/10.3389/fcell.2020.548335
  5. A Novel Bioengineered miR-127 Prodrug Suppresses the Growth and Metastatic Potential of Triple-Negative Breast Cancer Cells vol.80, pp.3, 2020, https://doi.org/10.1158/0008-5472.can-19-0656
  6. LncRNA SNHG1 contributes to the regulation of acute myeloid leukemia cell growth by modulating miR‐489‐3p/SOX12/Wnt/β‐catenin signaling vol.236, pp.1, 2017, https://doi.org/10.1002/jcp.29892
  7. SOX12 Promotes Stem Cell-Like Phenotypes and Osteosarcoma Tumor Growth by Upregulating JAGGED1 vol.2021, pp.None, 2017, https://doi.org/10.1155/2021/9941733