Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines

Yan,Xiuping; Luo,Hu; Zhou,Xiangdong; Zhu,Bingjing; Wang,Yuliang; Bian,Xiuwu

doi:10.3892/or.2013.2784

Identification of CD90 as a marker for lung cancer stem cells in A549 and H446 cell lines

Authors:
- Xiuping Yan
- Hu Luo
- Xiangdong Zhou
- Bingjing Zhu
- Yuliang Wang
- Xiuwu Bian
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Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China, Institute of Pathology and Southwest Cancer Center, The First Affiliated Hospital of Third Military Medical University, Chongqing 400038, P.R. China
Published online on: October 3, 2013 https://doi.org/10.3892/or.2013.2784
Pages: 2733-2740

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Abstract

Accumulating evidence supports that cancer stem cells (CSCs) are responsible for tumor initiation, progression, distal metastasis and even drug resistance. Although CD90 has been identified as a marker for several types of stem cells, such as liver CSCs, the potential role of CD90 as a marker for lung CSCs has yet to be fully characterized. Our previous study demonstrated that the lung cancer stem-like cells isolated from A549 tumor spheres, which were cultured in serum-free conditioned medium, had stronger proliferation and self-renewal abilities, and expressed higher levels of the stem cell markers Sox2 and Oct4 as compared to A549 adherent cells. In the present study, we identified CD90 as a novel surface marker of CSCs in lung cancer cells. Furthermore, we isolated CD90+ CSCs from lung cancer cell lines A549 and H446. Our results revealed that the CD90+ cells, but not the CD90- cells, from lung cancer cells displayed higher tumorigenic capacity. These findings suggest that CD90 could be a potential marker of lung CSCs and thus provide new insight into further therapeutic strategies of lung cancer.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
2	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar
3	Davidoff AJ, Tang M, Seal B and Edelman MJ: Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 28:2191–2197. 2010. View Article : Google Scholar : PubMed/NCBI
4	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar
5	Bautch VL: Cancer: Tumour stem cells switch sides. Nature. 468:770–771. 2010. View Article : Google Scholar : PubMed/NCBI
6	Wicha MS, Liu S and Dontu G: Cancer stem cells: an old idea - a paradigm shift. Cancer Res. 66:1883–1890; discussion 1895–1896. 2006. View Article : Google Scholar : PubMed/NCBI
7	Dean M, Fojo T and Bates S: Tumour stem cells and drug resistance. Nat Rev Cancer. 5:275–284. 2005. View Article : Google Scholar
8	Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI
9	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
10	Singh SK, Clarke ID, Terasaki M, et al: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI
11	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
12	Collins AT, Berry PA, Hyde C, Stower MJ and Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65:10946–10951. 2005. View Article : Google Scholar : PubMed/NCBI
13	Eramo A, Lotti F, Sette G, et al: Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 15:504–514. 2008. View Article : Google Scholar : PubMed/NCBI
14	Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
15	Galli R, Binda E, Orfanelli U, et al: Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res. 64:7011–7021. 2004. View Article : Google Scholar : PubMed/NCBI
16	Tirino V, Camerlingo R, Franco R, et al: The role of CD133 in the identification and characterisation of tumour-initiating cells in non-small-cell lung cancer. Eur J Cardiothorac Surg. 36:446–453. 2009. View Article : Google Scholar : PubMed/NCBI
17	Jiang F, Qiu Q, Khanna A, et al: Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 7:330–338. 2009. View Article : Google Scholar : PubMed/NCBI
18	Hirschmann-Jax C, Foster AE, Wulf GG, et al: A distinct ‘side population’ of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 101:14228–14233. 2004.
19	Meng X, Li M, Wang X, Wang Y and Ma D: Both CD133⁺ and CD133⁻ subpopulations of A549 and H446 cells contain cancer-initiating cells. Cancer Sci. 100:1040–1046. 2009.
20	Rege TA and Hagood JS: Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J. 20:1045–1054. 2006. View Article : Google Scholar : PubMed/NCBI
21	Cho RW, Wang X, Diehn M, et al: Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells. 26:364–371. 2008. View Article : Google Scholar : PubMed/NCBI
22	He J, Liu Y, Zhu T, et al: CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics. 11:M111.0107442012. View Article : Google Scholar : PubMed/NCBI
23	Yang ZF, Ho DW, Ng MN, et al: Significance of CD90⁺ cancer stem cells in human liver cancer. Cancer Cell. 13:153–166. 2008.
24	Yan YP, Luo H and Zhou XD: Isolation and identification of lung cancer stem like cells from human lung cancer cell line A549. J Third Mil Med Univ. 34:1153–1157. 2012.
25	Liu ZZ, Chen P, Lu ZD, Cui SD and Dong ZM: Enrichment of breast cancer stem cells using a keratinocyte serum-free medium. Chin Med J (Engl). 124:2934–2936. 2011.PubMed/NCBI
26	Hong X, Chedid K and Kalkanis SN: Glioblastoma cell line-derived spheres in serum-containing medium versus serum-free medium: a comparison of cancer stem cell properties. Int J Oncol. 41:1693–1700. 2012.PubMed/NCBI
27	Chase LG, Lakshmipathy U, Solchaga LA, Rao MS and Vemuri MC: A novel serum-free medium for the expansion of human mesenchymal stem cells. Stem Cell Res Ther. 1:82010. View Article : Google Scholar : PubMed/NCBI
28	Xiang R, Liao D, Cheng T, et al: Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer. Br J Cancer. 104:1410–1417. 2011. View Article : Google Scholar : PubMed/NCBI
29	Chen YC, Hsu HS, Chen YW, et al: Oct-4 expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells. PLoS One. 3:e26372008. View Article : Google Scholar : PubMed/NCBI
30	Huss WJ, Gray DR, Greenberg NM, Mohler JL and Smith GJ: Breast cancer resistance protein-mediated efflux of androgen in putative benign and malignant prostate stem cells. Cancer Res. 65:6640–6650. 2005. View Article : Google Scholar : PubMed/NCBI
31	Bao S, Wu Q, McLendon RE, et al: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 444:756–760. 2006. View Article : Google Scholar : PubMed/NCBI
32	Zhang Q, Shi S, Yen Y, Brown J, Ta JQ and Le AD: A subpopulation of CD133(+) cancer stem-like cells characterized in human oral squamous cell carcinoma confer resistance to chemotherapy. Cancer Lett. 289:151–160. 2010.
33	Li HZ, Yi TB and Wu ZY: Suspension culture combined with anticancer regimens for screening breast cancer stem cells. Med Hypotheses. 68:988–990. 2007. View Article : Google Scholar : PubMed/NCBI
34	Singh SK, Hawkins C, Clarke ID, et al: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI
35	Hermann PC, Huber SL, Herrler T, et al: Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell. 1:313–323. 2007. View Article : Google Scholar : PubMed/NCBI
36	Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T and Moriwaki H: Characterization of CD133⁺ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 351:820–824. 2006.
37	Bruno S, Bussolati B, Grange C, et al: CD133⁺ renal progenitor cells contribute to tumor angiogenesis. Am J Pathol. 169:2223–2235. 2006.
38	Shmelkov SV, Butler JM, Hooper AT, et al: CD133 expression is not restricted to stem cells, and both CD133⁺ and CD133⁻ metastatic colon cancer cells initiate tumors. J Clin Invest. 118:2111–2120. 2008.PubMed/NCBI
39	Wang J, Sakariassen PO, Tsinkalovsky O, et al: CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells. Int J Cancer. 122:761–768. 2008. View Article : Google Scholar : PubMed/NCBI
40	Joo KM, Kim SY, Jin X, et al: Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas. Lab Invest. 88:808–815. 2008. View Article : Google Scholar : PubMed/NCBI