Abstract
There is accumulating evidence that cancer stem cells (CSCs) play an important role in tumor progression. Novel strategies targeting CSCs have been widely researched. In the present study, we explored whether such CSCs existed in human ovarian cancer (OVCA) cell line and whether anti-CD44 antibody had effects on such subpopulation. We isolated and identified spheroid cells from SKOV-3. Then we used A3D8, an anti-CD44 mAb to treat spheroid cells with so-called “stemness”. Effects of A3D8 on spheroid cells’ biological behaviors were examined. Our findings showed that there was a small subpopulation that had so-called “stemness” in SKOV-3 cell line. Against spheroid cells, A3D8 can (1) inhibit cell proliferation; (2) change cell cycle distribution and expression of p21, CDK2 and cyclinA; (3) enhance cisplatin (DDP)-induced apoptosis; (4) promote cell differentiation; (5) inhibit clone formation efficiency; (6) reduce invasive efficacy; (7) inhibit tumorigenicity. Thus, to sum up points which we have just showed, spheroid cells isolated from SKOV-3 can be used as an appropriate in vitro model for relevant study of human ovarian CSCs. And our results reasoned that anti-CD44 therapy may become a potential promising strategy for OVCA treatment.
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Mimeault M, Batra S K. Functions of tumorigenic and migrating cancer progenitor cells in cancer progression and metastasis and their therapeutic implications. Cancer Metast Rev, 2007, 26: 203–214
Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance. Nat Rev Cancer, 2005, 5: 275–284
Mimeault M, Hauke R, Mehta P P, et al. Recent advances in cancer stem/progenitor cell research: Therapeutic implications for overcoming resistance to the most aggressive cancers. J Cell Mol Med, 2007, 11: 981–1011
Brabletz T, Jung A, Spaderna S, et al. Opinion: Migrating cancer stem cells—An integrated concept of malignant tumor progression. Nat Rev Cancer, 2005, 5: 744–749
Miller S J, Lavker R M, Sun T T. Interpreting epithelial cancer biology in the context of stem cells: Tumor properties and therapeutic implications. Biochim Biophys Acta, 2005, 1756: 25–52
Massard C, Deutsch E, Soria J C. Tumor stem cell-targeted treatment: Elimination or differentiation. Ann Oncol, 2006, 17: 1620–1624
Ponnusamy M P, Batra S K. Ovarian cancer: Emerging concept on cancer stem cells. J Ovarian Res, 2008, 1: 4–12
Misaghian N, Ligresti G, Steelman L S, et al. Targeting the leukemic stem cell: The Holy Grail of leukemia therapy. Leukemia, 2008, 23: 25–42
Charrad R S, Gadhoum Z, Qi J Y, et al. Effects of anti-CD44 monoclonal antibodies on differentiation and apoptosis of human myeloid leukemia cell lines. Blood, 2002, 99: 290–299
Gadhoum Z, Delaunay J, Maquarre E, et al. The effect of anti-CD44 monoclonal antibodies on differentiation and proliferation of human acute myeloid leukemia cells. Leuk Lymphoma, 2004, 45: 1501–1510
Gadhoum Z, Leibovitch M P, Qi J Y, et al. CD44: A new means to inhibit acute myeloid leukemia cell proliferation via p27 Kip1. Blood, 2004, 103: 1059–1068
Jin L Q, Hope K J, Zhai Q L, et al. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med, 2006, 12: 1167–1174
Zhang S, Balch C, Chan M W, et al. Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res, 2008, 68: 4311–4320
Bapat S A, Mali A M, Koppikar C B, et al. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovari an cancer. Cancer Res, 2005, 65: 3025–3029
Patel D D, Hale L P, Whichard L P, et al. Expression of CD44 molecules and CD44 ligands during human thymic fetal development: Expression of CD44 isoforms is developmentally regulated. Int Immunol, 1995, 7: 277–286
Li Z, Shen X T, Cao L, et al. Bone morphogenetic protein 2 improves patellar tendon healing by promoting migration and proliferation of tenocytes. Chin Sci Bull, 2011, 56: 1361–1369
Li H Z, Wang Y, Gao Y, et al. Effects of raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol Cancer Res, 2008, 6: 917–928
Matsui W, Wang Q, Barber J P, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res, 2008, 68: 190–197
Takubo K, Ohmura M, Azuma M, et al. Stem cell defects in ATM-deficient undifferentiated spermatogonia through DNA damage-induced cell-cycle arrest. Cell Stem Cell, 2008, 2: 170–182
Pascal L E, Oudes A J, Petersen T W, et al. Molecular and cellular characterization of ABCG2 in the prostate. BMC Urol, 2007, 7: 6–18
Croker A K, Goodale D, Chu J, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med, 2009, 13: 2236–2252
Wang J, Guo L P, Chen L Z. Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res, 2007, 67: 3716–3724
Kondo T, Setoguchi T, Taga T. Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line. Proc Natl Acad Sci USA, 2004, 101: 781–786
Maria M H, Alvin V N, Stephen L, et al. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res, 2007, 67: 4827–4833
Li Y F, Xiao B, Lai Z S, et al. Spheres isolated from Colo205 cell line possess cancer stem-like cells under serum-free culture condition. J South Med Univ, 2008, 28: 236–240
Dou J, Pan M, Wen P, et al. Isolation and identification of cancer stem-like cells from murine melanoma cell lines. Cell Mol Immunol, 2007, 4: 467–472
Wu C, Wei Q, Utomo V, et al. Side population cells isolated from mesenchymal neoplasms have tumor initiating potential. Cancer Res, 2007, 67: 8216–8222
Al-Hajj M, Wicha M S, Benito-Hernandez A. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 2003, 100: 3983–3988
Singh S K, Hawkins C, Clarke I D, et al. Identification of human brain tumour initiating cells. Nature, 2004, 432: 396–401
Hemmati H D, Nakano I, Lazareff J A, et al. Cancerous stem cells can arise from pediatric brain tumors. Proc Natl Acad Sci USA, 2003, 100: 15178–15183
Singh S K, Clarke I D, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res, 2003, 63: 5821–5828
Tan B T, Park C Y, Ailles L E, et al. The cancer stem cell hypothesis: A work in progress. Lab Invest, 2006, 86: 1203–1207
Gao G, Dou Q P. G(1) phase-dependent expression of bcl-2 mRNA and protein correlates with chemoresistance of human cancer cells. Mol Pharmacol, 2000, 58: 1001–1010
Makrydimas G, Zagorianakou N, Zagorianakou P, et al. CD44 family and gynaecological cancer. In Vivo, 2003, 17: 633–640
Cho E Y, Choi Y, Chae S W, et al. Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms. Pathol Int, 2006, 56: 62–70
Knowlton K, Mancini M, Creason S, et al. Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect. J Surg Res, 1998, 76: 22–26
Cannistra S A, Kansas G S, Niloff J, et al. Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44H. Cancer Res, 1993, 53: 3830–3838
Zada A A, Singh S M, Reddy V A, et al. Downregulation of c-Jun expression and cell cycle regulatory molecules in acute myeloid leukemia cells upon CD44 ligation. Oncogene, 2003, 22: 2296–2308
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Gu, C., Du, Y., Gao, Y. et al. Anti-CD44 mAb remodels biological behaviors of spheroid cells with stemness from human ovarian cancer cell line SKOV-3. Chin. Sci. Bull. 57, 1288–1297 (2012). https://doi.org/10.1007/s11434-012-5075-5
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DOI: https://doi.org/10.1007/s11434-012-5075-5