BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

CD166 promotes the cancer stem-like properties of primary epithelial ovarian cancer cells

  • Kim, Dae Kyoung (Department of Physiology, School of Medicine, Pusan National University) ;
  • Ham, Min Hee (Department of Physiology, School of Medicine, Pusan National University) ;
  • Lee, Seo Yul (Department of Physiology, School of Medicine, Pusan National University) ;
  • Shin, Min Joo (Department of Physiology, School of Medicine, Pusan National University) ;
  • Kim, Ye Eun (Department of Physiology, School of Medicine, Pusan National University) ;
  • Song, Parkyong (Department of Convergence Medicine, School of Medicine, Pusan National University) ;
  • Suh, Dong-Soo (Department of Obstetrics and Gynecology, School of Medicine, Pusan National University) ;
  • Kim, Jae Ho (Department of Physiology, School of Medicine, Pusan National University)
  • 투고 : 2020.05.13
  • 심사 : 2020.06.08
  • 발행 : 2020.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.

키워드

참고문헌

  1. Reid BM, Permuth JB and Sellers TA (2017) Epidemiology of ovarian cancer: a review. Cancer Biol Med 14, 9-32 https://doi.org/10.20892/j.issn.2095-3941.2016.0084
  2. Ahmed N, Kadife E, Raza A, Short M, Jubinsky PT and Kannourakis G (2020) Ovarian cancer, cancer stem cells and current treatment strategies: a potential role of magmas in the current treatment methods. Cells 9, 719 https://doi.org/10.3390/cells9030719
  3. Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G and Nikitin AY (2013) Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature 495, 241-245 https://doi.org/10.1038/nature11979
  4. Garson K and Vanderhyden BC (2015) Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm. Reproduction 149, R59-70 https://doi.org/10.1530/REP-14-0234
  5. Swart GW (2002) Activated leukocyte cell adhesion molecule (CD166/ALCAM): developmental and mechanistic aspects of cell clustering and cell migration. Eur J Cell Biol 81, 313-321 https://doi.org/10.1078/0171-9335-00256
  6. Tachezy M, Zander H, Gebauer F et al (2012) Activated leukocyte cell adhesion molecule (CD166)--its prognostic power for colorectal cancer patients. J Surg Res 177, e15-20 https://doi.org/10.1016/j.jss.2012.02.013
  7. Weidle UH, Eggle D, Klostermann S and Swart GW (2010) ALCAM/CD166: cancer-related issues. Cancer Genomics Proteomics 7, 231-243
  8. Jezierska A, Matysiak W and Motyl T (2006) ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy. Med Sci Monit 12, BR263-273
  9. Hansen AG, Arnold SA, Jiang M et al (2014) ALCAM/CD166 is a TGF-beta-responsive marker and functional regulator of prostate cancer metastasis to bone. Cancer Res 74, 1404-1415 https://doi.org/10.1158/0008-5472.CAN-13-1296
  10. Adisakwattana P, Suwandittakul N, Petmitr S, Wongkham S, Sangvanich P and Reamtong O (2015) ALCAM is a novel cytoplasmic membrane protein in TNF-alpha stimulated invasive cholangiocarcinoma cells. Asian Pac J Cancer Prev 16, 3849-3856 https://doi.org/10.7314/APJCP.2015.16.9.3849
  11. Yan M, Yang X, Wang L et al (2013) Plasma membrane proteomics of tumor spheres identify CD166 as a novel marker for cancer stem-like cells in head and neck squamous cell carcinoma. Mol Cell Proteomics 12, 3271-3284 https://doi.org/10.1074/mcp.M112.025460
  12. Jiao J, Hindoyan A, Wang S et al (2012) Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells. PLoS One 7, e42564 https://doi.org/10.1371/journal.pone.0042564
  13. von Lersner A, Droesen L and Zijlstra A (2019) Modulation of cell adhesion and migration through regulation of the immunoglobulin superfamily member ALCAM/CD166. Clin Exp Metastasis 36, 87-95 https://doi.org/10.1007/s10585-019-09957-2
  14. van Kempen LC, Nelissen JM, Degen WG et al (2001) Molecular basis for the homophilic activated leukocyte cell adhesion molecule (ALCAM)-ALCAM interaction. J Biol Chem 276, 25783-25790 https://doi.org/10.1074/jbc.M011272200
  15. Swart GW, Lunter PC, Kilsdonk JW and Kempen LC (2005) Activated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide of melanoma cell clustering and cell migration? Cancer Metastasis Rev 24, 223-236 https://doi.org/10.1007/s10555-005-1573-0
  16. Tudor C, te Riet J, Eich C et al (2014) Syntenin-1 and ezrin proteins link activated leukocyte cell adhesion molecule to the actin cytoskeleton. J Biol Chem 289, 13445-13460 https://doi.org/10.1074/jbc.M113.546754
  17. Yu W, Wang J, Ma L et al (2014) CD166 plays a pro--carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT. Oncol Rep 32, 677-683 https://doi.org/10.3892/or.2014.3226
  18. Ma L, Wang J, Lin J, Pan Q, Yu Y and Sun F (2014) Cluster of differentiation 166 (CD166) regulated by phosphatidylinositide 3-Kinase (PI3K)/AKT signaling to exert its anti-apoptotic role via yes-associated protein (YAP) in liver cancer. J Biol Chem 289, 6921-6933 https://doi.org/10.1074/jbc.M113.524819
  19. Jia G, Wang X, Yan M, Chen W and Zhang P (2016) CD166-mediated epidermal growth factor receptor phosphorylation promotes the growth of oral squamous cell carcinoma. Oral Oncol 59, 1-11 https://doi.org/10.1016/j.oraloncology.2016.05.010
  20. Seo EJ, Kwon YW, Jang IH et al (2016) Autotaxin regulates maintenance of ovarian cancer stem cells through lysophosphatidic acid-mediated autocrine mechanism. Stem Cells 34, 551-564 https://doi.org/10.1002/stem.2279
  21. Choi EJ, Seo EJ, Kim DK et al (2016) FOXP1 functions as an oncogene in promoting cancer stem cell-like characteristics in ovarian cancer cells. Oncotarget 7, 3506-3519 https://doi.org/10.18632/oncotarget.6510
  22. Kang KT, Kwon YW, Kim DK et al (2018) TRRAP stimulates the tumorigenic potential of ovarian cancer stem cells. BMB Rep 51, 514-519 https://doi.org/10.5483/BMBRep.2018.51.10.042
  23. Parsons JT (2003) Focal adhesion kinase: the first ten years. J Cell Sci 116, 1409-1416 https://doi.org/10.1242/jcs.00373
  24. Westhoff MA, Serrels B, Fincham VJ, Frame MC and Carragher NO (2004) SRC-mediated phosphorylation of focal adhesion kinase couples actin and adhesion dynamics to survival signaling. Mol Cell Biol 24, 8113-8133 https://doi.org/10.1128/MCB.24.18.8113-8133.2004
  25. Seo EJ, Kim DK, Jang IH et al (2016) Hypoxia-NOTCH1-SOX2 signaling is important for maintaining cancer stem cells in ovarian cancer. Oncotarget 7, 55624-55638 https://doi.org/10.18632/oncotarget.10954
  26. Djirackor L, Kalirai H, Coupland SE and Petrovski G (2019) CD166high uveal melanoma cells represent a subpopulation with enhanced migratory capacity. Invest Ophthalmol Vis Sci 60, 2696-2704 https://doi.org/10.1167/iovs.18-26431
  27. Xiao M, Wang X, Yan M and Chen W (2016) A systematic evaluation for the potential translation of CD166-related expression as a cancer biomarker. Expert Rev Mol Diagn 16, 925-932 https://doi.org/10.1080/14737159.2016.1211932
  28. Degen WG, van Kempen LC, Gijzen EG et al (1998) MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule). Am J Pathol 152, 805-813
  29. Devis L, Moiola CP, Masia N et al (2017) Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early-stage endometrioid endometrial cancer. J Pathol 241, 475-487 https://doi.org/10.1002/path.4851
  30. Sun Y, Lin H, Qu S et al (2019) Downregulation of CD166 inhibits invasion, migration, and EMT in the radio-resistant human nasopharyngeal carcinoma cell line CNE-2R. Cancer Manag Res 11, 3593-3602 https://doi.org/10.2147/CMAR.S194685
  31. Ferragut F, Cagnoni AJ, Colombo LL et al (2019) Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth. Biochim Biophys Acta Mol Cell Res 1866, 1338-1352 https://doi.org/10.1016/j.bbamcr.2019.03.010
  32. Gilsanz A, Sanchez-Martin L, Gutierrez-Lopez MD et al (2013) ALCAM/CD166 adhesive function is regulated by the tetraspanin CD9. Cell Mol Life Sci 70, 475-493 https://doi.org/10.1007/s00018-012-1132-0