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Tumor-suppressive activity of sTRAIL on circulating CD44+ cells in patients with non-small cell lung cancer

  • Yan-Bin Sun , Guang-Hao Sun , Shun Xu and Jing-Jing Xu EMAIL logo
Published/Copyright: September 25, 2019

Abstract

Circulating CD44+ cells have been identified as a prognostic marker for patients with non-small cell lung cancer (NSCLC). Serum tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) is involved in the pathophysiology of many cancers. However, no previous studies have shown the roles of sTRAIL in circulating CD44+ cells in the blood of NSCLC patients. We detected circulating CD44+ cells and sTRAIL levels in blood samples from NSCLC patients using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Anti-tumor roles of TRAIL in CD44+ cells were confirmed using a CCK-8 assay and mouse models. A higher number of circulating CD44+ cells were identified in NSCLC patients compared with healthy control individuals. In addition, we confirmed the anti-tumor roles and mechanisms of TRAIL in CD44+ cells both in vitro and in vivo. Our results indicate that (1) there is a negative correlation between sTRAIL and circulating CD44+ cells in NSCLC patients and (2) CD44+ cells have cancer stem cell properties and are more sensitive than CD44 cells to TRAIL.

Keywords: CD44; NSCLC; P53; prognosis; TRAIL
  1. Conflict of interest statement: The authors have no conflict of interest.

References

Cheng, S.W., Tsai, H.W., Lin, Y.J., Cheng, P.N., Chang, Y.C., Yen, C.J., Huang, H.P., Chuang, Y.P., Chang, T.T., Lee, C.T., et al. (2013). Lin28B is an oncofetal circulating cancer stem cell-like marker associated with recurrence of hepatocellular carcinoma. PLoS One 8, e80053.10.1371/journal.pone.0080053Search in Google Scholar PubMed PubMed Central

Dingli, D. and Michor, F. (2006). Successful therapy must eradicate cancer stem cells. Stem Cells 24, 2603–2610.10.1634/stemcells.2006-0136Search in Google Scholar PubMed

Dou, Y., Wang, Y., Xu, J., Li, Z., Sun, P., and Meng, Q. (2014). Experiment research on inhibition of glioma with sTRAIL in vitro. Artif. Cells Nanomed. Biotechnol. 42, 186–191.10.3109/21691401.2013.794350Search in Google Scholar PubMed

Fan, S.T., Yang, Z.F., Ho, D.W., Ng, M.N., Yu, W.C., and Wong, J. (2011). Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann. Surg. 254, 569–576.10.1097/SLA.0b013e3182300a1dSearch in Google Scholar PubMed

Fitzgerald, T.L. and McCubrey, J.A. (2014). Pancreatic cancer stem cells: association with cell surface markers, prognosis, resistance, metastasis and treatment. Adv. Biol. Regul. 56, 45–50.10.1016/j.jbior.2014.05.001Search in Google Scholar PubMed

Gao, Y., Foster, R., Yang, X., Feng, Y., Shen, J.K., Mankin, H.J., Hornicek, F.J., Amiji, M.M., and Duan, Z. (2015). Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer. Oncotarget 6, 9313–9326.10.18632/oncotarget.3220Search in Google Scholar PubMed PubMed Central

Janisiewicz, A.M., Shin, J.H., Murillo-Sauca, O., Kwok, S., Le, Q.T., Kong, C., Kaplan, M.J., and Sunwoo, J.B. (2012). CD44+ cells have cancer stem cell-like properties in nasopharyngeal carcinoma. Int. Forum. Allergy Rhinol. 2, 465–470.10.1002/alr.21068Search in Google Scholar PubMed

Jiang, H., Zhao, W., and Shao, W. (2014). Prognostic value of CD44 and CD44v6 expression in patients with non-small cell lung cancer: meta-analysis. Tumour Biol. 35, 7383–7389.10.1007/s13277-014-2150-3Search in Google Scholar PubMed

Jin, Z., McDonald 3rd, E.R., Dicker, D.T., and El-Deiry, W.S. (2004). Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J. Biol. Chem. 279, 35829–35839.10.1074/jbc.M405538200Search in Google Scholar PubMed

Kargi, A., Yalcin, A.D., Erin, N., Savas, B., Polat, H.H., and Gorczynski, R.M. (2012). IL8 and serum soluble TRAIL levels following anti-VEGF monoclonal antibody treatment in patients with metastatic colon cancer. Clin. Lab. 58, 501–505.Search in Google Scholar

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. Med. 14, 450–460.10.1016/j.molmed.2008.08.003Search in Google Scholar PubMed

Lee, S.H., Kim, M.J., Kim, D.W., Kang, C.D., and Kim, S.H. (2013). Amurensin G enhances the susceptibility to tumor necrosis factor-related apoptosis-inducing ligand-mediated cytotoxicity of cancer stem-like cells of HCT-15 cells. Cancer Sci. 104, 1632–1639.10.1111/cas.12299Search in Google Scholar

Leung, E.L., Fiscus, R.R., Tung, J.W., Tin, V.P., Cheng, L.C., Sihoe, A.D., Fink, L.M., Ma, Y., and Wong, M.P. (2010). Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties. PLoS One 5, e14062.10.1371/journal.pone.0014062Search in Google Scholar

Li, M., Zhang, B., Zhang, Z., Liu, X., Qi, X., Zhao, J., Jiang, Y., Zhai, H., Ji, Y., and Luo, D. (2014). Stem cell-like circulating tumor cells indicate poor prognosis in gastric cancer. Biomed. Res. Int. 2014, 981261.10.1155/2014/981261Search in Google Scholar

Molina, J.R., Yang, P., Cassivi, S.D., Schild, S.E., and Adjei, A.A. (2008). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo. Clin. Proc. 83, 584–594.10.1016/S0025-6196(11)60735-0Search in Google Scholar

Naor, D., Nedvetzki, S., Golan, I., Melnik, L., and Faitelson, Y. (2002). CD44 in cancer. Crit. Rev. Clin. Lab. Sci. 39, 527–579.10.1080/10408360290795574Search in Google Scholar PubMed

Noor, A., Umelo, I.A., Kronenberger, P., Giron, P., De Vlieghere, E., De Wever, O., Teugels, E., and De Grève, J. (2018). Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer. Oncotarget 9, 28731–28744.10.1200/JCO.2017.35.15_suppl.e14104Search in Google Scholar

Ponta, H., Sherman, L., and Herrlich, P.A. (2003). CD44: from adhesion molecules to signalling regulators. Nat. Rev. Mol. Cell Biol. 4, 33–45.10.1038/nrm1004Search in Google Scholar PubMed

Reya, T., Morrison, S.J., Clarke, M.F., and Weissman, I.L. (2001). Stem cells, cancer, and cancer stem cells. Nature 414, 105–111.10.1038/35102167Search in Google Scholar PubMed

Siegel, R.L., Miller, K.D., and Jemal, A. (2018). Cancer statistics, 2018. CA Cancer J. Clin. 68, 7–30.10.3322/caac.21442Search in Google Scholar PubMed

Tinhofer, I., Saki, M., Niehr, F., Keilholz, U., and Budach, V. (2014). Cancer stem cell characteristics of circulating tumor cells. Int. J. Radiat. Biol. 90, 622–627.10.3109/09553002.2014.886798Search in Google Scholar PubMed

Tornese, G., Iafusco, D., Monasta, L., Agnoletto, C., Tisato, V., Ventura, A., Zauli, G., and Secchiero, P. (2014). The levels of circulating TRAIL at the onset of type 1 diabetes are markedly decreased in patients with ketoacidosis and with the highest insulin requirement. Acta Diabetol. 51, 239–246.10.1007/s00592-013-0507-5Search in Google Scholar

Wiley, S.R., Schooley, K., Smolak, P.J., Din, W.S., Huang, C.P., Nicholl, J.K., Sutherland, G.R., Smith, T.D., Rauch, C., Smith, C.A., et al. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.10.1016/1074-7613(95)90057-8Search in Google Scholar

Xia, P., Song, C.L., Liu, J.F., Wang, D., and Xu, X.Y. (2015). Prognostic value of circulating CD133+ cells in patients with gastric cancer. Cell Prolif. 48, 311–317.10.1111/cpr.12175Search in Google Scholar PubMed PubMed Central

Yang, N., Yao, S., and Liu, D. (2018). Tumor necrosis factor-related apoptosis-inducing ligand additive with iodine-131 of inhibits non-small cell lung cancer cells through promoting apoptosis. Oncol. Lett. 16, 276–284.10.3892/ol.2018.8635Search in Google Scholar PubMed PubMed Central

Yu, R., Albarenque, S.M., Cool, R.H., Quax, W.J., Mohr, A., and Zwacka, R.M. (2014). DR4 specific TRAIL variants are more efficacious than wild-type TRAIL in pancreatic cancer. Cancer Biol. Ther. 15, 1658–1666.10.4161/15384047.2014.972183Search in Google Scholar PubMed PubMed Central

Zhang, L. and Fang, B. (2005). Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene. Ther. 12, 228–237.10.1038/sj.cgt.7700792Search in Google Scholar PubMed

Zhang, X., Wang, L., Liu, Y., Huang, W., and Cheng, D. (2018). MiR-760 enhances TRAIL sensitivity in non-small cell lung cancer via targeting the protein FOXA1. Biomed. Pharmacother. 99, 523–529.10.1016/j.biopha.2018.01.076Search in Google Scholar PubMed

Received: 2019-08-08
Accepted: 2019-09-10
Published Online: 2019-09-25
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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