Skip to main content

Cancer Stem Cells in Gynecologic Cancer

  • Chapter
  • First Online:
Stem Cells in Cancer: Should We Believe or Not?

Abstract

Gynecological cancer is currently the sixth leading cause of death among women. Despite screening campaigns, early diagnosis and vaccination against Human Papilloma Virus, gynecological cancers -mostly ovarian cancer- are often diagnosed at advanced stages. Although the high effectiveness of existing medical treatments, during long term therapy, often seem insufficient to achieve the cure or the disease. This is due to the presence of metastases at the time of diagnosis and to the development of resistance to cytostatic treatments and further recurrences.

The discovery and understanding of Cancer Stem Cells (CSCs) leads to an encouraging outlook on the future treatment of these patients. Within the perspective of the CSCs concept model, gynecological CSCs have specific genetic and epigenetic variations that give them capabilities to undergo asymmetric cell divisions, ensuring new generations of CSCs and of more differentiated gynecological cancer cells. As a result of these biological capabilities, CSCs can mediate gynecological cancers occurrence, resistance to treatment and recurrence.

In this review we discuss emerging evidences supporting the existence of CSCs in ovarian, endometrial and cervical cancers. Focus is given to recent molecular and genomic advances regarding the characterization of abnormal signaling cascades in these three types of gynecological CSCs. We also discuss the current knowledge on genetic and epigenetic changes in gynecological cancers and CSCs, and how researchers propose that these cellular changes influence CSCs in their control of cancer development and recurrence.

We also discuss advances in medical treatment of gynecological cancer using CSCs as a therapeutic target.

Mellídez, Juan Carlos and Santos, Maria C. have contributed equally to this work.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Aguilar-Gallardo C, Rutledge EC, Martinez-Arroyo AM, Hidalgo JJ, Domingo S, Simon C (2012) Overcoming challenges of ovarian cancer stem cells: novel therapeutic approaches. Stem Cell Rev 8(3):994–1010. doi:10.1007/s12015-011-9344-5

    PubMed  CAS  Google Scholar 

  2. Ahmed N, Abubaker K, Findlay J, Quinn M (2013) Cancerous ovarian stem cells: obscure targets for therapy but relevant to chemoresistance. J Cell Biochem 114(1):21–34. doi:10.1002/jcb.24317

    PubMed  CAS  Google Scholar 

  3. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100(7):3983–3988. doi:10.1073/pnas.0530291100

    PubMed Central  PubMed  CAS  Google Scholar 

  4. Alison MR, Lin WR, Lim SM, Nicholson LJ (2012) Cancer stem cells: in the line of fire. Cancer Treat Rev 38(6):589–598. doi:10.1016/j.ctrv.2012.03.003

    PubMed  CAS  Google Scholar 

  5. Alvero AB, Chen R, Fu HH, Montagna M, Schwartz PE, Rutherford T, Silasi DA, Steffensen KD, Waldstrom M, Visintin I, Mor G (2009) Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance. Cell Cycle 8(1):158–166

    PubMed Central  PubMed  CAS  Google Scholar 

  6. Alvero AB, Montagna MK, Holmberg JC, Craveiro V, Brown D, Mor G (2011) Targeting the mitochondria activates two independent cell death pathways in ovarian cancer stem cells. Mol Cancer Ther 10(8):1385–1393. doi:10.1158/1535-7163.MCT-11-0023

    PubMed Central  PubMed  CAS  Google Scholar 

  7. Anderson NS, Turner L, Livingston S, Chen R, Nicosia SV, Kruk PA (2009) Bcl-2 expression is altered with ovarian tumor progression: an immunohistochemical evaluation. J Ovarian Res 2(1):16. doi:10.1186/1757-2215-2-16

    PubMed Central  PubMed  Google Scholar 

  8. Auersperg N, Wong AS, Choi KC, Kang SK, Leung PC (2001) Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev 22(2):255–288. doi:10.1210/er.22.2.255

    PubMed  CAS  Google Scholar 

  9. Balch C, Matei DE, Huang TH, Nephew KP (2010) Role of epigenomics in ovarian and endometrial cancers. Epigenomics 2(3):419–447. doi:10.2217/epi.10.19

    PubMed  CAS  Google Scholar 

  10. Baley J, Li J (2012) MicroRNAs and ovarian function. J Ovarian Res 5(1):8. doi:10.1186/1757-2215-5-8

    PubMed Central  PubMed  CAS  Google Scholar 

  11. Bapat SA (2010) Human ovarian cancer stem cells. Reproduction 140(1):33–41. doi:10.1530/REP-09-0389

    PubMed  CAS  Google Scholar 

  12. Bapat SA (2012) Epigenetic regulation of cancer stem cell gene expression. Subcell Biochem 61:419–434. doi:10.1007/978-94-007-4525-4_18

    Google Scholar 

  13. Bapat SA, Jin V, Berry N, Balch C, Sharma N, Kurrey N, Zhang S, Fang F, Lan X, Li M, Kennedy B, Bigsby RM, Huang TH, Nephew KP (2010) Multivalent epigenetic marks confer microenvironment-responsive epigenetic plasticity to ovarian cancer cells. Epigenetics 5(8):716–729

    PubMed Central  PubMed  CAS  Google Scholar 

  14. Bapat SA, Mali AM, Koppikar CB, Kurrey NK (2005) Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer. Cancer Res 65(8):3025–3029. doi:10.1158/0008-5472.CAN-04-3931

    PubMed  CAS  Google Scholar 

  15. Barker N, Clevers H (2007) Tracking down the stem cells of the intestine: strategies to identify adult stem cells. Gastroenterology 133(6):1755–1760. doi:10.1053/j.gastro.2007.10.029

    PubMed  CAS  Google Scholar 

  16. Bauerschlag D, Brautigam K, Moll R, Sehouli J, Mustea A, Salehin D, Krajewska M, Reed JC, Maass N, Hampton GM, Meinhold-Heerlein I (2013) Systematic analysis and validation of differential gene expression in ovarian serous adenocarcinomas and normal ovary. J Cancer Res Clin Oncol 139(2):347–355. doi:10.1007/s00432-012-1334-8

    PubMed  Google Scholar 

  17. Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD (2009) Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesion molecule-specific immunotherapy. Int J Gynecol Cancer 19(5):860–866. doi:10.1111/IGC.0b013e3181a8331f

    PubMed  Google Scholar 

  18. Berman ML (2003) Future directions in the surgical management of ovarian cancer. Gynecol Oncol 90(2 Pt 2):S33–S39. doi:10.1016/S0090-8258(03)00342-1

    PubMed  Google Scholar 

  19. Berry NB, Bapat SA (2008) Ovarian cancer plasticity and epigenomics in the acquisition of a stem-like phenotype. J Ovarian Res 1:8. doi:10.1186/1757-2215-1-8

    PubMed Central  PubMed  Google Scholar 

  20. Burgos-Ojeda D, Rueda BR, Buckanovich RJ (2012) Ovarian cancer stem cell markers: prognostic and therapeutic implications. Cancer Lett 322(1):1–7. doi:10.1016/j.canlet.2012.02.002

    PubMed  CAS  Google Scholar 

  21. Cai N, Wang YD, Zheng PS (2013) The microRNA-302-367 cluster suppresses the proliferation of cervical carcinoma cells through the novel target AKT1. RNA 19(1):85–95. doi:10.1261/rna.035295.112

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Cervello I, Mirantes C, Santamaria X, Dolcet X, Matias-Guiu X, Simon C (2011) Stem cells in human endometrium and endometrial carcinoma. Int J Gynecol Pathol 30(4):317–327. doi:10.1097/PGP.0b013e3182102754

    PubMed  Google Scholar 

  23. Chan RW, Schwab KE, Gargett CE (2004) Clonogenicity of human endometrial epithelial and stromal cells. Biol Reprod 70(6):1738–1750. doi:10.1095/biolreprod.103.024109

    PubMed  CAS  Google Scholar 

  24. Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, Liu J (2009) ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol 22(6):817–823. doi:10.1038/modpathol.2009.35

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Chen ZG (2010) Small-molecule delivery by nanoparticles for anticancer therapy. Trends Mol Med 16(12):594–602. doi:10.1016/j.molmed.2010.08.001

    PubMed  CAS  Google Scholar 

  26. Cheng W, Jiang Y, Liu C, Shen O, Tang W, Wang X (2010) Identification of aberrant promoter hypomethylation of HOXA10 in ovarian cancer. J Cancer Res Clin Oncol 136(8):1221–1227. doi:10.1007/s00432-010-0772-4

    PubMed  CAS  Google Scholar 

  27. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL, Wahl GM (2006) Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66(19):9339–9344. doi:10.1158/0008-5472.CAN-06-3126

    PubMed  CAS  Google Scholar 

  28. Clevers H (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17(3):313–319. doi:10.1038/nm.2304

    PubMed  CAS  Google Scholar 

  29. Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R (2009) CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 27(12):2875–2883. doi:10.1002/stem.236

    PubMed  CAS  Google Scholar 

  30. De Stefano I, Battaglia A, Zannoni GF, Prisco MG, Fattorossi A, Travaglia D, Baroni S, Renier D, Scambia G, Ferlini C, Gallo D (2011) Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts. Cancer Chemother Pharmacol 68(1):107–116. doi:10.1007/s00280-010-1462-2

    PubMed  CAS  Google Scholar 

  31. Dellinger TH, Planutis K, Tewari KS, Holcombe RF (2012) Role of canonical Wnt signaling in endometrial carcinogenesis. Expert Rev Anticancer Ther 12(1):51–62. doi:10.1586/era.11.194

    PubMed  CAS  Google Scholar 

  32. Deonarain MP, Kousparou CA, Epenetos AA (2009) Antibodies targeting cancer stem cells: a new paradigm in immunotherapy? MAbs 1(1):12–25

    PubMed Central  PubMed  Google Scholar 

  33. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, Furth EE, Lee WM, Enders GH, Mendell JT, Thomas-Tikhonenko A (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 38(9):1060–1065. doi:10.1038/ng1855

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Dong P, Kaneuchi M, Watari H, Hamada J, Sudo S, Ju J, Sakuragi N (2011) MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer 10:99. doi:10.1186/1476-4598-10-99

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Donnenberg VS, Landreneau RJ, Donnenberg AD (2007) Tumorigenic stem and progenitor cells: implications for the therapeutic index of anti-cancer agents. J Control Release 122(3):385–391. doi:10.1016/j.jconrel.2007.05.005

    PubMed Central  PubMed  CAS  Google Scholar 

  36. Dreesen O, Brivanlou AH (2007) Signaling pathways in cancer and embryonic stem cells. Stem Cell Rev 3(1):7–17. doi:10.1007/s12015-007-0004-8

    PubMed  CAS  Google Scholar 

  37. Fabian A, Vereb G, Szollosi J (2013) The hitchhikers guide to cancer stem cell theory: markers, pathways and therapy. Cytometry A 83(1):62–71. doi:10.1002/cyto.a.22206

    PubMed  Google Scholar 

  38. Fang D, Nguyen TK, Leishear K, Finko R, Kulp AN, Hotz S, Van Belle PA, Xu X, Elder DE, Herlyn M (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65(20):9328–9337. doi:10.1158/0008-5472.CAN-05-1343

    PubMed  CAS  Google Scholar 

  39. Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D (2010) GLOBOCAN 2008 v1.2: cancer incidence and mortality worldwide: IARC CancerBase No. 10. IARC Press. http://globocan.iarc.fr. 2012

  40. Ferrandina G, Bonanno G, Pierelli L, Perillo A, Procoli A, Mariotti A, Corallo M, Martinelli E, Rutella S, Paglia A, Zannoni G, Mancuso S, Scambia G (2008) Expression of CD133-1 and CD133-2 in ovarian cancer. International Journal Gynecological Cancer 18(3):506–514. doi:10.1111/j.1525-1438.2007.01056.x

    CAS  Google Scholar 

  41. Ferrandina G, Martinelli E, Petrillo M, Prisco MG, Zannoni G, Sioletic S, Scambia G (2009) CD133 antigen expression in ovarian cancer. Bmc Cancer 9:221. doi:10.1186/1471-2407-9-221

    PubMed Central  PubMed  Google Scholar 

  42. Fiegl H, Windbichler G, Mueller-Holzner E, Goebel G, Lechner M, Jacobs IJ, Widschwendter M (2008) HOXA11 DNA methylation–a novel prognostic biomarker in ovarian cancer. Int J Cancer 123(3):725–729. doi:10.1002/ijc.23563

    PubMed  CAS  Google Scholar 

  43. Fong MY, Kakar SS (2010) The role of cancer stem cells and the side population in epithelial ovarian cancer. Histology Histopathology 25(1):113–120

    PubMed  CAS  Google Scholar 

  44. Friel AM, Sergent PA, Patnaude C, Szotek PP, Oliva E, Scadden DT, Seiden MV, Foster R, Rueda BR (2008) Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells. Cell Cycle 7(2):242–249

    PubMed  CAS  Google Scholar 

  45. Friel AM, Zhang L, Curley MD, Therrien VA, Sergent PA, Belden SE, Borger DR, Mohapatra G, Zukerberg LR, Foster R, Rueda BR (2010) Epigenetic regulation of CD133 and tumorigenicity of CD133 positive and negative endometrial cancer cells. Reprod Biol Endocrinol 8:147. doi:10.1186/1477-7827-8-147

    PubMed Central  PubMed  CAS  Google Scholar 

  46. Gallagher MF, Heffron CC, Laios A, O’Toole SA, Ffrench B, Smyth PC, Flavin RJ, Elbaruni SA, Spillane CD, Martin CM, Sheils OM, O’Leary JJ (2012) Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples. J Ovarian Res 5(1):2. doi:10.1186/1757-2215-5-2

    PubMed Central  PubMed  CAS  Google Scholar 

  47. Gao Q, Geng L, Kvalheim G, Gaudernack G, Suo Z (2009) Identification of cancer stem-like side population cells in ovarian cancer cell line OVCAR-3. Ultrastruct Pathol 33(4):175–181. doi:10.1080/01913120903086072

    PubMed  Google Scholar 

  48. Gargett CE (2004) Stem cells in gynaecology. Aust N Z J Obstet Gynaecol 44(5):380–386. doi:10.1111/j.1479-828X.2004.00290.x

    PubMed  Google Scholar 

  49. Gargett CE (2006) Identification and characterisation of human endometrial stem/progenitor cells. Aust N Z J Obstet Gynaecol 46(3):250–253. doi:10.1111/j.1479-828X.2006.00582.x

    PubMed  Google Scholar 

  50. Giuffrida D, Rogers IM (2010) Targeting cancer stem cell lines as a new treatment of human cancer. Recent Pat Anticancer Drug Discov 5(3):205–218

    PubMed  CAS  Google Scholar 

  51. Goff BA, Mandel LS, Melancon CH, Muntz HG (2004) Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA 291(22):2705–2712. doi:10.1001/jama.291.22.2705

    PubMed  CAS  Google Scholar 

  52. Gotte M, Greve B, Kelsch R, Muller-Uthoff H, Weiss K, Kharabi Masouleh B, Sibrowski W, Kiesel L, Buchweitz O (2011) The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1. Int J Cancer 129(8):2042–2049. doi:10.1002/ijc.25856

    PubMed  Google Scholar 

  53. Gotte M, Wolf M, Staebler A, Buchweitz O, Kelsch R, Schuring AN, Kiesel L (2008) Increased expression of the adult stem cell marker Musashi-1 in endometriosis and endometrial carcinoma. J Pathol 215(3):317–329. doi:10.1002/path.2364

    PubMed  CAS  Google Scholar 

  54. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481(7381):306–313. doi:10.1038/nature10762

    PubMed Central  PubMed  CAS  Google Scholar 

  55. Green JM, Alvero AB, Kohen F, Mor G (2009) 7-(O)-Carboxymethyl daidzein conjugated to N-t-Boc-hexylenediamine: a novel compound capable of inducing cell death in epithelial ovarian cancer stem cells. Cancer Biol Ther 8(18):1747–1753

    PubMed Central  PubMed  CAS  Google Scholar 

  56. Grommes C, Landreth G, Heneka M (2004) Antineoplastic effects of peroxisome proliferatoractivated receptor γ agonists. Lancet Oncol 5(7):419–429. doi:10.1016/s1470-2045(04)01509-8

    PubMed  CAS  Google Scholar 

  57. Gu TT, Liu SY, Zheng PS (2012) Cytoplasmic NANOG-positive stromal cells promote human cervical cancer progression. Am J Pathol 181(2):652–661. doi:10.1016/j.ajpath.2012.04.008

    PubMed  CAS  Google Scholar 

  58. Guddati AK (2012) Ovarian cancer stem cells: elusive targets for chemotherapy. Med Oncol 29(5):3400–3408. doi:10.1007/s12032-012-0252-6

    PubMed  CAS  Google Scholar 

  59. Guo Y, Nemeth J, O’Brien C, Susa M, Liu X, Zhang Z, Choy E, Mankin H, Hornicek F, Duan Z (2010) Effects of siltuximab on the IL-6-induced signaling pathway in ovarian cancer. Clin Cancer Res 16(23):5759–5769. doi:10.1158/1078-0432.CCR-10-1095

    PubMed  CAS  Google Scholar 

  60. Gupta PB, Chaffer CL, Weinberg RA (2009) Cancer stem cells: mirage or reality? Nat Med 15(9):1010–1012. doi:10.1038/nm0909-1010

    PubMed  CAS  Google Scholar 

  61. Hadnagy A, Gaboury L, Beaulieu R, Balicki D (2006) SP analysis may be used to identify cancer stem cell populations. Exp Cell Res 312(19):3701–3710. doi:10.1016/j.yexcr.2006.08.030

    PubMed  CAS  Google Scholar 

  62. Hamilton TC, Connolly DC, Nikitin AY, Garson K, Vanderhyden BC (2003) Translational research in ovarian cancer: a must. Int J Gynecol Cancer 13:220–230. doi:10.1111/j.1525-1438.2003.13350.x

    PubMed  Google Scholar 

  63. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013

    PubMed  CAS  Google Scholar 

  64. Heintz AP, Odicino F, Maisonneuve P, Beller U, Benedet JL, Creasman WT, Ngan HY, Pecorelli S (2003) Carcinoma of the ovary. Int J Gynaecol Obstet 83(Suppl 1):135–166. doi:10.1016/S0020-7292(03)90118-4

    PubMed  Google Scholar 

  65. Herfs M, Vargas SO, Yamamoto Y, Howitt BE, Nucci MR, Hornick JL, Mckeon FD, Xian W, Crum CP (2013) A novel blueprint for ‘top down’ differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia. J Pathol 229(3):460–468. doi:10.1002/Path.4110

    PubMed  Google Scholar 

  66. Hermann PC, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C (2007) Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1(3):313–323. doi:10.1016/j.stem.2007.06.002

    PubMed  CAS  Google Scholar 

  67. Hu J, Yuan R (2011) The expression levels of stem cell markers importin13, c-kit, CD146, and telomerase are decreased in endometrial polyps. Med Sci Monit 17(8):BR221–BR227

    PubMed Central  PubMed  CAS  Google Scholar 

  68. Hubbard SA, Friel AM, Kumar B, Zhang L, Rueda BR, Gargett CE (2009) Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res 69(21):8241–8248. doi:10.1158/0008-5472.CAN-08-4808

    PubMed  CAS  Google Scholar 

  69. Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, Calin GA, Menard S, Croce CM (2007) MicroRNA signatures in human ovarian cancer. Cancer Res 67(18):8699–8707. doi:10.1158/0008-5472.CAN-07-1936

    PubMed  CAS  Google Scholar 

  70. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi:10.3322/caac.20107

    PubMed  Google Scholar 

  71. Juarez-Moreno K, Erices R, Beltran AS, Stolzenburg S, Cuello-Fredes M, Owen GI, Qian H, Blancafort P (2013) Breaking through an epigenetic wall: re-activation of Oct4 by KRAB-containing designer zinc finger transcription factors. Epigenetics 8(2):164–176. doi:10.4161/epi.23503

    PubMed Central  PubMed  CAS  Google Scholar 

  72. Kato K (2012) Endometrial cancer stem cells: a new target for cancer therapy. Anticancer Res 32(6):2283–2293

    PubMed  CAS  Google Scholar 

  73. Kato K (2012) Stem cells in human normal endometrium and endometrial cancer cells: characterization of side population cells. Kaohsiung J Med Sci 28(2):63–71. doi:10.1016/j.kjms.2011.06.028

    PubMed  Google Scholar 

  74. Kato K, Kuhara A, Yoneda T, Inoue T, Takao T, Ohgami T, Dan L, Kuboyama A, Kusunoki S, Takeda S, Wake N (2011) Sodium butyrate inhibits the self-renewal capacity of endometrial tumor side-population cells by inducing a DNA damage response. Mol Cancer Ther 10(8):1430–1439. doi:10.1158/1535-7163.MCT-10-1062

    PubMed  CAS  Google Scholar 

  75. Kato K, Takao T, Kuboyama A, Tanaka Y, Ohgami T, Yamaguchi S, Adachi S, Yoneda T, Ueoka Y, Kato K, Hayashi S, Asanoma K, Wake N (2010) Endometrial cancer side-population cells show prominent migration and have a potential to differentiate into the mesenchymal cell lineage. Am J Pathol 176(1):381–392. doi:10.2353/ajpath.2010.090056

    PubMed Central  PubMed  CAS  Google Scholar 

  76. Kelly ZL, Michael A, Butler-Manuel S, Pandha HS, Morgan RG (2011) HOX genes in ovarian cancer. J Ovarian Res 4(1):16. doi:10.1186/1757-2215-4-16

    PubMed Central  PubMed  CAS  Google Scholar 

  77. Koeffler HP (2003) Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res 9(1):1–9

    PubMed  CAS  Google Scholar 

  78. Koh J, Lee SB, Park H, Lee HJ, Cho NH, Kim J (2012) Susceptibility of CD24(+) ovarian cancer cells to anti-cancer drugs and natural killer cells. Biochem Biophys Res Commun 427(2):373–378. doi:10.1016/j.bbrc.2012.09.067

    PubMed  CAS  Google Scholar 

  79. Kristiansen G, Denkert C, Schluns K, Dahl E, Pilarsky C, Hauptmann S (2002) CD24 is expressed in ovarian cancer and is a new independent prognostic marker of patient survival. Am J Pathol 161(4):1215–1221. doi:10.1016/S0002-9440(10)64398-2

    PubMed Central  PubMed  CAS  Google Scholar 

  80. Kryczek I, Liu S, Roh M, Vatan L, Szeliga W, Wei S, Banerjee M, Mao Y, Kotarski J, Wicha MS, Liu R, Zou W (2012) Expression of aldehyde dehydrogenase and CD133 defines ovarian cancer stem cells. Int J Cancer 130(1):29–39. doi:10.1002/ijc.25967

    PubMed Central  PubMed  CAS  Google Scholar 

  81. Kurtz JE, Dufour P (2010) Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside. Expert Opin Biol Ther 10(6):951–958. doi:10.1517/14712598.2010.482098

    PubMed  CAS  Google Scholar 

  82. Kyo S, Maida Y, Inoue M (2011) Stem cells in endometrium and endometrial cancer: accumulating evidence and unresolved questions. Cancer Lett 308(2):123–133. doi:10.1016/j.canlet.2011.05.015

    PubMed  CAS  Google Scholar 

  83. Lacey JV, Sherman ME (2009) Ovarian neoplasia. In: Robboy SJ, Bentley RC, Russell P, Anderson MC, Mutter GL, Prat J (eds) Robboy’s pathology of the female reproductive tract, vol 1, 2nd edn.Churchill Livingstone Elsevier, Oxford. p 601

    Google Scholar 

  84. Landen CN Jr, Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, Miller LD, Mejia PV, Jennings NB, Gershenson DM, Bast RC Jr, Coleman RL, Lopez-Berestein G, Sood AK (2010) Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther 9(12):3186–3199. doi:10.1158/1535-7163.MCT-10-0563

    PubMed Central  PubMed  CAS  Google Scholar 

  85. Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177(3):1053–1064. doi:10.2353/ajpath.2010.100105

    PubMed Central  PubMed  Google Scholar 

  86. Liao X, Siu MK, Au CW, Wong ES, Chan HY, Ip PP, Ngan HY, Cheung AN (2009) Aberrant activation of hedgehog signaling pathway in ovarian cancers: effect on prognosis, cell invasion and differentiation. Carcinogenesis 30(1):131–140. doi:10.1093/carcin/bgn230

    PubMed  CAS  Google Scholar 

  87. Lichtenauer UD, Shapiro I, Geiger K, Quinkler M, Fassnacht M, Nitschke R, Ruckauer KD, Beuschlein F (2008) Side population does not define stem cell-like cancer cells in the adrenocortical carcinoma cell line NCI h295R. Endocrinology 149(3):1314–1322. doi:10.1210/en.2007-1001

    PubMed  CAS  Google Scholar 

  88. Liu D, Zhou P, Zhang L, Gong W, Huang G, Zheng Y, He F (2012) HDAC1/DNMT3A-containing complex is associated with suppression of Oct4 in cervical cancer cells. Biochemistry Biokhimiia 77(8):934–940. doi:10.1134/S0006297912080159

    PubMed  CAS  Google Scholar 

  89. Lopez J, Ruiz G, Organista-Nava J, Gariglio P, Garcia-Carranca A (2012) Human papillomavirus infections and cancer stem cells of tumors from the uterine cervix. Open Virol J 6:232–240. doi:10.2174/1874357901206010232

    PubMed Central  PubMed  Google Scholar 

  90. Lu B, Hu M, Liu K, Peng J (2010) Cytotoxicity of berberine on human cervical carcinoma HeLa cells through mitochondria, death receptor and MAPK pathways, and in-silico drug-target prediction. Toxicol In Vitro 24(6):1482–1490. doi:10.1016/j.tiv.2010.07.017

    PubMed  CAS  Google Scholar 

  91. Lu X, Lin F, Fang H, Yang X, Qin L (2011) Expression of a putative stem cell marker Musashi-1 in endometrium. Histol Histopathol 26(9):1127–1133

    PubMed  CAS  Google Scholar 

  92. Luo L, Zeng J, Liang B, Zhao Z, Sun L, Cao D, Yang J, Shen K (2011) Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome. Exp Mol Pathol 91(2):596–602. doi:10.1016/j.yexmp.2011.06.005

    PubMed  CAS  Google Scholar 

  93. Mak VC, Siu MK, Wong OG, Chan KK, Ngan HY, Cheung AN (2012) Dysregulated stemness-related genes in gynecological malignancies. Histol Histopathol 27(9):1121–1130

    PubMed  CAS  Google Scholar 

  94. Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M (2008) CD44 and EpCAM: cancer-initiating cell markers. Curr Mol Med 8(8):784–804. doi:10.2174/156652408786733667

    PubMed  CAS  Google Scholar 

  95. Marks PA, Xu WS (2009) Histone deacetylase inhibitors: potential in cancer therapy. J Cell Biochem 107(4):600–608. doi:10.1002/jcb.22185

    PubMed Central  PubMed  CAS  Google Scholar 

  96. Massuger L, Roelofsen T, Ham M, Bulten J (2010) The origin of serous ovarian cancer may be found in the uterus: a novel hypothesis. Med Hypotheses 74(5):859–861. doi:10.1016/j.mehy.2009.11.029

    PubMed  Google Scholar 

  97. Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G (2008) Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: a Hoosier Oncology Group trial. Cancer 113(4):723–732. doi:10.1002/cncr.23605

    PubMed  CAS  Google Scholar 

  98. Mehrazma M, Madjd Z, Kalantari E, Panahi M, Hendi A, Shariftabrizi A (2012) Expression of stem cell markers, CD133 and CD44, in pediatric solid tumors: a study using tissue microarray. Fetal Pediatr Pathol. doi:10.3109/15513815.2012.701266

    PubMed  Google Scholar 

  99. Meng E, Long B, Sullivan P, McClellan S, Finan MA, Reed E, Shevde L, Rocconi RP (2012) CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival. Clin Exp Metastasis 29(8):939–948. doi:10.1007/s10585-012-9482-4

    PubMed  CAS  Google Scholar 

  100. Micci F, Weimer J, Haugom L, Skotheim RI, Grunewald R, Abeler VM, Silins I, Lothe RA, Trope CG, Arnold N, Heim S (2009) Reverse painting of microdissected chromosome 19 markers in ovarian carcinoma identifies a complex rearrangement map. Genes Chromosomes Cancer 48(2):184–193. doi:10.1002/gcc.20628

    PubMed  CAS  Google Scholar 

  101. Mimeault M, Batra SK (2008) Recent progress on tissue-resident adult stem cell biology and their therapeutic implications. Stem Cell Rev 4(1):27–49. doi:10.1007/s12015-008-9008-2

    PubMed  Google Scholar 

  102. Min KJ, So KA, Ouh YT, Hong JH, Lee JK (2012) The effects of DNA methylation and epigenetic factors on the expression of CD133 in ovarian cancers. J Ovarian Res 5(1):28. doi:10.1186/1757-2215-5-28

    PubMed Central  PubMed  CAS  Google Scholar 

  103. Mor G, Yin G, Chefetz I, Yang Y, Alvero A (2011) Ovarian cancer stem cells and inflammation. Cancer Biol Ther 11(8):708–713

    PubMed Central  PubMed  Google Scholar 

  104. Mundhenke C, Weigel MT, Sturner KH, Roesel F, Meinhold-Heerlein I, Bauerschlag DO, Schem C, Hilpert F, Jonat W, Maass N (2008) Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects. J Cancer Res Clin Oncol 134(12):1397–1405. doi:10.1007/s00432-008-0408-0

    PubMed  CAS  Google Scholar 

  105. Murdoch WJ, Martinchick JF (2004) Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: carcinogenic implication and chemoprevention. Exp Biol Med 229(6):546–552

    CAS  Google Scholar 

  106. Murdoch WJ, McDonnel AC (2002) Roles of the ovarian surface epithelium in ovulation and carcinogenesis. Reproduction 123(6):743–750. doi:10.1530/reprod/123.6.743

    PubMed  CAS  Google Scholar 

  107. Obermair A, Fuller A, Lopez-Varela E, van Gorp T, Vergote I, Eaton L, Fowler J, Quinn M, Hammond I, Marsden D, Proietto A, Carter J, Davy M, Tripcony L, Abu-Rustum N (2007) A new prognostic model for FIGO stage 1 epithelial ovarian cancer. Gynecol Oncol 104(3):607–611. doi:10.1016/j.ygyno.2006.09.021

    PubMed  Google Scholar 

  108. Ohm JE, McGarvey KM, Yu X, Cheng L, Schuebel KE, Cope L, Mohammad HP, Chen W, Daniel VC, Yu W, Berman DM, Jenuwein T, Pruitt K, Sharkis SJ, Watkins DN, Herman JG, Baylin SB (2007) A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nat Genet 39(2):237–242. doi:10.1038/ng1972

    PubMed Central  PubMed  CAS  Google Scholar 

  109. Opipari AW Jr, Tan L, Boitano AE, Sorenson DR, Aurora A, Liu JR (2004) Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 64(2):696–703

    PubMed  CAS  Google Scholar 

  110. Orian-Rousseau V (2010) CD44, a therapeutic target for metastasising tumours. Eur J Cancer 46(7):1271–1277. doi:10.1016/j.ejca.2010.02.024

    PubMed  CAS  Google Scholar 

  111. Pan Y, Huang X (2008) Epithelial ovarian cancer stem cells-a review. Int J Clin Exp Med 1(3):260–266

    PubMed Central  PubMed  CAS  Google Scholar 

  112. Patrawala L, Calhoun T, Schneider-Broussard R, Zhou J, Claypool K, Tang DG (2005) Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer Res 65(14):6207–6219. doi:10.1158/0008-5472.CAN-05-0592

    PubMed  CAS  Google Scholar 

  113. Peracchio C, Alabiso O, Valente G, Isidoro C (2012) Involvement of autophagy in ovarian cancer: a working hypothesis. J Ovarian Res 5(1):22. doi:10.1186/1757-2215-5-22

    PubMed Central  PubMed  CAS  Google Scholar 

  114. Phuc PV, Khuong TTT, Dong LV, Kiet TD, Giang TT, Ngoc PK (2010) Isolation and characterization of breast cancer stem cells from malignant tumours in Vietnamese women. J Ovarian Res 1(4):163–169

    Google Scholar 

  115. Ponnusamy MP, Batra SK (2008) Ovarian cancer: emerging concept on cancer stem cells. J Ovarian Res 1(1):4. doi:10.1186/1757-2215-1-4

    PubMed Central  PubMed  Google Scholar 

  116. Ponnusamy MP, Seshacharyulu P, Vaz A, Dey P, Batra SK (2011) MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells. J Ovarian Res 4(1):7. doi:10.1186/1757-2215-4-7

    PubMed Central  PubMed  CAS  Google Scholar 

  117. Prince ME, Sivanandan R, Kaczorowski A, Wolf GT, Kaplan MJ, Dalerba P, Weissman IL, Clarke MF, Ailles LE (2007) Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A 104(3):973–978. doi:10.1073/pnas.0610117104

    PubMed Central  PubMed  CAS  Google Scholar 

  118. Ray A, Meng E, Reed E, Shevde LA, Rocconi RP (2011) Hedgehog signaling pathway regulates the growth of ovarian cancer spheroid forming cells. Int J Oncol 39(4):797–804. doi:10.3892/ijo.2011.1093

    PubMed  CAS  Google Scholar 

  119. Reichert JM (2012) Marketed therapeutic antibodies compendium. MAbs 4(3):413–415. doi:10.4161/mabs.19931

    PubMed Central  PubMed  Google Scholar 

  120. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R (2007) Identification and expansion of human colon-cancer-initiating cells. Nature 445(7123):111–115. doi:10.1038/nature05384

    PubMed  CAS  Google Scholar 

  121. Ries LAG, Melbert D, Krapcho M, Mariotto A, Miller BA, Feuer EJ, Clegg L, Horner MJ, Howlader N, Eisner MP, Reichman M, Edwards BK (2007) SEER cancer statistics review, 1975–2004. National Cancer Institute. Bethesda, MD., p 103. http://seer.cancer.gov/archive/csr/1975_2004/results_merged/sect_01_overview.pdf

  122. Riman T, Nilsson S, Persson IR (2004) Review of epidemiological evidence for reproductive and hormonal factors in relation to the risk of epithelial ovarian malignancies. Acta Obstet Gynecol Scand 83(9):783–795. doi:10.1111/j.0001-6349.2004.00550.x

    PubMed  Google Scholar 

  123. Ruiz-Vela A, Aguilar-Gallardo C, Martinez-Arroyo AM, Soriano-Navarro M, Ruiz V, Simon C (2011) Specific unsaturated fatty acids enforce the transdifferentiation of human cancer cells toward adipocyte-like cells. Stem Cell Rev 7(4):898–909. doi:10.1007/s12015-011-9253-7

    PubMed  CAS  Google Scholar 

  124. Sabbatini P, Aghajanian C, Dizon D, Anderson S, Dupont J, Brown JV, Peters WA, Jacobs A, Mehdi A, Rivkin S, Eisenfeld AJ, Spriggs D (2004) Phase II study of CT-2103 in patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. J Clin Oncol 22(22):4523–4531. doi:10.1200/jco.2004.12.043

    PubMed  CAS  Google Scholar 

  125. Samardzija C, Quinn M, Findlay JK, Ahmed N (2012) Attributes of Oct4 in stem cell biology: perspectives on cancer stem cells of the ovary. J Ovarian Res 5(1):37. doi:10.1186/1757-2215-5-37

    PubMed Central  PubMed  Google Scholar 

  126. Sarry JE, Murphy K, Perry R, Sanchez PV, Secreto A, Keefer C, Swider CR, Strzelecki AC, Cavelier C, Recher C, Mansat-De Mas V, Delabesse E, Danet-Desnoyers G, Carroll M (2011) Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rgammac-deficient mice. J Clin Invest 121(1):384–395. doi:10.1172/JCI41495

    PubMed Central  PubMed  CAS  Google Scholar 

  127. Sato A, Ishiwata T, Matsuda Y, Yamamoto T, Asakura H, Takeshita T, Naito Z (2012) Expression and role of nestin in human cervical intraepithelial neoplasia and cervical cancer. Int J Oncol 41(2):441–448. doi:10.3892/ijo.2012.1473

    PubMed Central  PubMed  CAS  Google Scholar 

  128. Schatton T, Frank MH (2008) Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res 21(1):39–55. doi:10.1111/j.1755-148X.2007.00427.x

    PubMed Central  PubMed  CAS  Google Scholar 

  129. Seeber LM, van Diest PJ (2012) Epigenetics in ovarian cancer. Methods Mol Biol 863:253–269. doi:10.1007/978-1-61779-612-8_15

    PubMed  CAS  Google Scholar 

  130. Seimetz D (2011) Novel monoclonal antibodies for cancer treatment: the trifunctional antibody catumaxomab (removab). J Cancer 2:309–316

    PubMed Central  PubMed  CAS  Google Scholar 

  131. Sell S (2004) Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 51(1):1–28. doi:10.1016/j.critrevonc.2004.04.007

    PubMed  Google Scholar 

  132. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics for Hispanics/Latinos, 2012. CA Cancer J Clin 62(5):283–298. doi:10.3322/caac.21153

    PubMed  Google Scholar 

  133. Silva IA, Bai S, McLean K, Yang K, Griffith K, Thomas D, Ginestier C, Johnston C, Kueck A, Reynolds RK, Wicha MS, Buckanovich RJ (2011) Aldehyde dehydrogenase in combination with CD133 defines angiogenic ovarian cancer stem cells that portend poor patient survival. Cancer Res 71(11):3991–4001. doi:10.1158/0008-5472.CAN-10-3175

    PubMed Central  PubMed  CAS  Google Scholar 

  134. Slomovitz BM, Coleman RL (2012) The PI3K/AKT/mTOR pathway as a therapeutic target in endometrial cancer. Clin Cancer Res 18(21):5856–5864. doi:10.1158/1078-0432.CCR-12-0662

    PubMed  CAS  Google Scholar 

  135. Smith LM, Nesterova A, Ryan MC, Duniho S, Jonas M, Anderson M, Zabinski RF, Sutherland MK, Gerber HP, Van Orden KL, Moore PA, Ruben SM, Carter PJ (2008) CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br J Cancer 99(1):100–109. doi:10.1038/sj.bjc.6604437

    PubMed Central  PubMed  CAS  Google Scholar 

  136. Soignet SL, Benedetti F, Fleischauer A, Parker BA, Truglia JA, Ra Crisp M, Warrell RP Jr (1998) Clinical study of 9-cis retinoic acid (LGD1057) in acute promyelocytic leukemia. Leukemia 12(10):1518–1521

    PubMed  CAS  Google Scholar 

  137. Soltysova A, Altanerova V, Altaner C (2005) Cancer stem cells. Neoplasma 52(6):435–440

    PubMed  CAS  Google Scholar 

  138. Spizzo G, Went P, Dirnhofer S, Obrist P, Moch H, Baeuerle PA, Mueller-Holzner E, Marth C, Gastl G, Zeimet AG (2006) Overexpression of epithelial cell adhesion molecule (Ep-CAM) is an independent prognostic marker for reduced survival of patients with epithelial ovarian cancer. Gynecol Oncol 103(2):483–488. doi:10.1016/j.ygyno.2006.03.035

    PubMed  CAS  Google Scholar 

  139. Steg AD, Bevis KS, Katre AA, Ziebarth A, Dobbin ZC, Alvarez RD, Zhang K, Conner M, Landen CN (2012) Stem cell pathways contribute to clinical chemoresistance in ovarian cancer. Clin Cancer Res 18(3):869–881. doi:10.1158/1078-0432.CCR-11-2188

    PubMed Central  PubMed  CAS  Google Scholar 

  140. Su PH, Lin YW, Huang RL, Liao YP, Lee HY, Wang HC, Chao TK, Chen CK, Chan MW, Chu TY, Yu MH, Lai HC (2013) Epigenetic silencing of PTPRR activates MAPK signaling, promotes metastasis and serves as a biomarker of invasive cervical cancer. Oncogene 32(1):15–26. doi:10.1038/onc.2012.29

    PubMed  CAS  Google Scholar 

  141. Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, Dombkowski D, Preffer F, Maclaughlin DT, Donahoe PK (2006) Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A 103(30):11154–11159. doi:10.1073/pnas.0603672103

    PubMed Central  PubMed  CAS  Google Scholar 

  142. Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, Gordon SA, Shimada Y, Wang TC (2009) Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells 27(5):1006–1020. doi:10.1002/stem.30

    PubMed Central  PubMed  CAS  Google Scholar 

  143. Theriault BL, Shepherd TG (2011) On the path to translation: highlights from the 2010 Canadian Conference on Ovarian Cancer Research. J Ovarian Res 4(1):10. doi:10.1186/1757-2215-4-10

    PubMed Central  PubMed  Google Scholar 

  144. Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, La Noce M, Laino L, De Francesco F, Papaccio G (2013) Cancer stem cells in solid tumors: an overview and new approaches for their isolation and characterization. FASEB J 27(1):13–24. doi:10.1096/fj.12-218222

    PubMed  CAS  Google Scholar 

  145. Titus-Ernstoff L, Perez K, Cramer DW, Harlow BL, Baron JA, Greenberg ER (2001) Menstrual and reproductive factors in relation to ovarian cancer risk. Br J Cancer 84(5):714–721. doi:10.1054/bjoc.2000.1596

    PubMed Central  PubMed  CAS  Google Scholar 

  146. Vathipadiekal V, Saxena D, Mok SC, Hauschka PV, Ozbun L, Birrer MJ (2012) Identification of a potential ovarian cancer stem cell gene expression profile from advanced stage papillary serous ovarian cancer. PLoS One 7(1):e29079. doi:10.1371/journal.pone.0029079

    PubMed Central  PubMed  CAS  Google Scholar 

  147. Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, Newman J, Bronson RT, Crowley D, Stone JR, Jaenisch R, Sharp PA, Jacks T (2008) Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 132(5):875–886. doi:10.1016/j.cell.2008.02.019

    PubMed Central  PubMed  CAS  Google Scholar 

  148. Vergote IB, Kaern J, Abeler VM, Pettersen EO, De Vos LN, Trope CG (1993) Analysis of prognostic factors in stage I epithelial ovarian carcinoma: importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse. Am J Obstet Gynecol 169(1):40–52

    PubMed  CAS  Google Scholar 

  149. Vignati S, Albertini V, Rinaldi A, Kwee I, Riva C, Oldrini R, Capella C, Bertoni F, Carbone GM, Catapano CV (2006) Cellular and molecular consequences of peroxisome proliferator-activated receptor-gamma activation in ovarian cancer cells. Neoplasia 8(10):851–861. doi:10.1593/neo.06433

    PubMed Central  PubMed  CAS  Google Scholar 

  150. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768. doi:10.1038/nrc2499

    PubMed  CAS  Google Scholar 

  151. Visvader JE, Lindeman GJ (2012) Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10(6):717–728. doi:10.1016/j.stem.2012.05.007

    PubMed  CAS  Google Scholar 

  152. Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJF, Peto J, Meijer CJLM, Munoz N (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189(1):12–19. doi:10.1002/(Sici)1096-9896(199909)189:1<12::Aid-Path431>3.0.Co;2-F

    PubMed  CAS  Google Scholar 

  153. Wang H, Jin P, Sabatino M, Ren J, Civini S, Bogin V, Ichim TE, Stroncek DF (2012) Comparison of endometrial regenerative cells and bone marrow stromal cells. J Transl Med 10(1):207. doi:10.1186/1479-5876-10-207

    PubMed Central  PubMed  CAS  Google Scholar 

  154. Wang Y, van der Zee M, Fodde R, Blok LJ (2010) Wnt/Beta-catenin and sex hormone signaling in endometrial homeostasis and cancer. Oncotarget 1(7):674–684

    PubMed Central  PubMed  Google Scholar 

  155. Wang YC, Yo YT, Lee HY, Liao YP, Chao TK, Su PH, Lai HC (2012) ALDH1-bright epithelial ovarian cancer cells are associated with CD44 expression, drug resistance, and poor clinical outcome. Am J Pathol 180(3):1159–1169. doi:10.1016/j.ajpath.2011.11.015

    PubMed  Google Scholar 

  156. Wingo SN, Gallardo TD, Akbay EA, Liang MC, Contreras CM, Boren T, Shimamura T, Miller DS, Sharpless NE, Bardeesy N, Kwiatkowski DJ, Schorge JO, Wong KK, Castrillon DH (2009) Somatic LKB1 mutations promote cervical cancer progression. PLoS One 4(4):e5137. doi:10.1371/journal.pone.0005137

    PubMed Central  PubMed  Google Scholar 

  157. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, Stack MS, Friedl P (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9(8):893–904. doi:10.1038/ncb1616

    PubMed  CAS  Google Scholar 

  158. Ye F, Zhou C, Cheng Q, Shen J, Chen H (2008) Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer 8:108. doi:10.1186/1471-2407-8-108

    PubMed Central  PubMed  Google Scholar 

  159. Yee GP, de Souza P, Khachigian LM (2013) Current and potential treatments for cervical cancer. Curr Cancer Drug Targets 13(2):205–220

    PubMed  CAS  Google Scholar 

  160. Zavesky L, Jancarkova N, Kohoutova M (2011) Ovarian cancer: origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease. Neoplasma 58(6):457–468. doi:10.4149/neo_2011_06_457

    PubMed  CAS  Google Scholar 

  161. Zeng B, Hu J, Yuan R, Hu L, Zhong L, Kang K (2012) Increased expression of importin13 in endometriosis and endometrial carcinoma. Med Sci Monit 18(6):CR361–CR367

    PubMed Central  PubMed  CAS  Google Scholar 

  162. Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K, Johnstone CN, Megraw MS, Adams S, Lassus H, Huang J, Kaur S, Liang S, Sethupathy P, Leminen A, Simossis VA, Sandaltzopoulos R, Naomoto Y, Katsaros D, Gimotty PA, DeMichele A, Huang Q, Butzow R, Rustgi AK, Weber BL, Birrer MJ, Hatzigeorgiou AG, Croce CM, Coukos G (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A 105(19):7004–7009. doi:10.1073/pnas.0801615105

    PubMed Central  PubMed  CAS  Google Scholar 

  163. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, Nephew KP (2008) Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res 68(11):4311–4320. doi:10.1158/0008-5472.CAN-08-0364

    PubMed Central  PubMed  CAS  Google Scholar 

  164. American Cancer Society (2013) Cancer facts and figures 2013. Corporate Center: American Cancer Society Inc. NW, Atlanta, GA, p 62 (online. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf

  165. World Health Organization (2010) HPV and cervical cancer (HPV Information Center). Human papillomavirus and related cancers in the world. Summary Report 2010. http://www.who.int/hpvcentre/en

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Barroso, J.C.M., Santos, M.C. (2014). Cancer Stem Cells in Gynecologic Cancer. In: Grande, E., Antón Aparicio, L. (eds) Stem Cells in Cancer: Should We Believe or Not?. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8754-3_13

Download citation

Publish with us

Policies and ethics