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Journal of Ovarian Research

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Open Access 01-12-2016 | Research

Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer

Authors: Irma Virant-Klun, Natasa Kenda-Suster, Spela Smrkolj

Published in: Journal of Ovarian Research | Issue 1/2016

Abstract

Background

In previous studies it has been found that in cell cultures of human adult ovaries there is a population of small stem cells with diameters of 2–4 μm, which are present mainly in the ovarian surface epithelium and are comparable to very small embryonic-like stem cells (VSELs) from bone marrow. These cells are not observed by histopathologists in the ovarian tissue due to their small size and unknown clinical significance. Because these cells express a degree of pluripotency, they might be involved in the manifestation of ovarian cancer. Therefore we studied the ovarian tissue sections in women with borderline ovarian cancer and serous ovarian carcinoma to perhaps identify the small putative stem cells in situ.

Methods

In 27 women with borderline ovarian cancer and 20 women with high-grade serous ovarian carcinoma the ovarian tissue sections were stained, per standard practice, with eosin and hematoxylin staining and on NANOG, SSEA-4 and SOX2 markers, related to pluripotency, using immunohistochemistry. We focused on the presence and localization of small putative stem cells with diameters of up to 5 μm and with the nuclei spread over nearly the full cell volume.

Results

In ovarian sections of both borderline ovarian cancer and serous ovarian carcinoma patients we were able to identify the presence of small round cells complying with the above criteria. Some of these small cells were NANOG-positive, were located among epithelial cells in the ovarian surface epithelium and as a single cell or groups of cells/clusters in typical “chambers”, were found only in the presence of ovarian cancer and not in healthy ovaries and are comparable to those in fetal ovaries. We envision that these small cells could be related to NANOG-positive tumor-like structures and oocyte-like cells in similar “chambers” found in sections of cancerous ovaries, which could support their stemness and pluripotency. Further immunohistochemistry revealed a similar population of SSEA-4 and SOX2-positive cells.

Conclusions

We may conclude that putative small stem cells expressing markers, related to pluripotency, are present in the ovarian tissue sections of women with borderline ovarian cancer and high-grade serous ovarian carcinoma thus indicating their potential involvement in ovarian cancer.

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Bapat SA, Mali AM, Koppikar CB, Kurrey NK. Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cencer. Cancer Res. 2005;65:3025–9.PubMed

Murphy SK. Targeting ovarian cancer-initiating cells. Anticancer Agents Med Chem. 2010;10:157–63.CrossRefPubMed

Vochem R, Einenkel J, Horn LC, Ruschpler P. Importance of the tumor stem cell hypothesis for understanding ovarian cancer. Pathologe. 2014;35:361–70.CrossRefPubMed

Zhang QH, Dou HT, Xu P, Zhuang SC, Liu PS. Tumor recurrence and drug resistance properties of side population cells in high grade ovary cancer. Drug Res (Stuttg). 2015;65:153–7.

Martínez-Serrano MJ, Caballero-Baños M, Vilella L, Pahisa J, Martínez-Roman S. Is sphere assay useful for the identification of cancer initiating cells in the ovary? Int J Gynecol Cancer. 2015;25:12–7.CrossRefPubMed

Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, et al. ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol. 2009;22:817–23.PubMedPubMedCentral

Douville J, Beaulieu R, Balicki D. ALDH1 as a Functional Marker of Cancer Stem and Progenitor Cells. Stem Cells Dev. 2009;18:17–25.CrossRefPubMed

Penumatsa K, Edassery SL, Barua A, Bradaric MJ, Luborsky JL. Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors. J Ovarian Res. 2010;3:28.CrossRefPubMedPubMedCentral

Auersperg N. The stem-cell profile of ovarian surface epithelium is reproduced in the oviductal fimbriae, with increased stem-cell marker density in distal parts of the fimbriae. Int J Gynecol Pathol. 2013;32:444–53.CrossRefPubMed

10.

Kuroda T, Hirohashi Y, Torigoe T, Yasuda K, Takahashi A, Asanuma H, et al. ALDH1-high ovarian cancer stem-like cells can be isolated from serous and clear cell adenocarcinoma cells, and ALDH1 high expression is associated with poor prognosis. PLoS One. 2013;8:e65158.CrossRefPubMedPubMedCentral

11.

Amsterdam A, Raanan C, Schreiber L, Freyhan O, Schechtman L, Givol D. Localization of the stem cell markers LGR5 and Nanog in the normal and the cancerous human ovary and their inter-relationship. Acta Histochem. 2013;115:330–8.CrossRefPubMed

12.

Flesken-Nikitin A, Hwang CI, Cheng CY, Michurina TV, Enikolopov G, Nikitin AY. Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche. Nature. 2013;495:241–5.CrossRefPubMedPubMedCentral

13.

Capel B. Ovarian epithelium regeneration by LGR5(+) cells. Nature Cell Biol. 2014;16:743–4.CrossRefPubMed

14.

Ng A, Tan S, Singh G, Rizk P, Swathi Y, Tan TZ, et al. Lgr5 marks stem/progenitor cells in ovary and tubal epithelia. Nature Cell Biol. 2014;16:745–57.CrossRefPubMed

15.

Sun Y, Jia X, Wu X. High Expressions of Lgr5 and ALDH1 in Primary Epithelial Ovarian Cancer Correlate with Advanced Tumor Stage and Grade as well as Poor Prognosis of the Patients. Gynecol Obstet Invest. 2015 June 20. [Epub ahead of print].

16.

Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, Dinulescu DM, Connolly D, Foster R, et al. Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci USA. 2006;103:11154–9.CrossRefPubMedPubMedCentral

17.

Yasuda H, Torigoe T, Morita R, Kuroda T, Takahashi A, Matsuzaki J, et al. Ovarian cancer stem cells are enriched in side population and aldehyde dehydrogenase bright overlapping population. PLoS One. 2013;8:e68187.CrossRefPubMedPubMedCentral

18.

Zeng J, Ruan J, Luo L, Shi J, Cui Q, Yang J, et al. Molecular portraits of heterogeneity related to cancer stem cells in human ovarian cancer. Int J Gynecol Cancer. 2014;24:29–35.CrossRefPubMed

19.

Virant-Klun I, Zech N, Rozman P, Vogler A, Cvjeticanin B, Klemenc P, et al. Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes. Differentiation. 2008;76:843–56.CrossRefPubMed

20.

Virant-Klun I, Rozman P, Cvjeticanin B, Vrtacnik-Bokal E, Novakovic S, Rülicke T, et al. Parthenogenetic embryo-like structures in the human ovarian surface epithelium cell culture in postmenopausal women with no naturally present follicles and oocytes. Stem Cells Dev. 2009;18:1109.CrossRef

21.

Virant-Klun I, Skutella T, Hren M, Gruden K, Cvjeticanin B, Vogler A, et al. Isolation of small SSEA-4-positive putative stem cells from the ovarian surface epithelium in adult human ovaries by two different methods. Biomed Res Int. 2013;2013:690415.PubMedPubMedCentral

22.

Virant-Klun I, Skutella T, Kubista M, Vogler A, Sinkovec J, Meden-Vrtovec H. Expression of pluripotency and oocyte-related genes in single putative stem cells from human adult ovarian surface epithelium cultured in vitro in the presence of follicular fluid. Biomed Res Int. 2013;2013:861460.PubMedPubMedCentral

23.

Virant-Klun I, Skutella T, Stimpfel M, Sinkovec J. Ovarian surface epithelium in patients with severe ovarian infertility: a potential source of cells expressing markers of pluripotent/multipotent stem cells. J Biomed Biotechnol. 2011;2011:381928.CrossRefPubMedPubMedCentral

24.

Virant-Klun I, Stimpfel M, Cvjeticanin B, Vrtacnik-Bokal E, Skutella T. Small SSEA-4-positive cells from human ovarian cell cultures: related to embryonic stem cells and germinal lineage? J Ovarian Res. 2013;6:24.CrossRefPubMedPubMedCentral

25.

Parte S, Bhartiya D, Telang J, Daithankar V, Salvi V, Zaveri K, et al. Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary. Stem Cells Dev. 2011;20:1451–64.CrossRefPubMedPubMedCentral

26.

Joo BS, Jung IK, Park MJ, Joo JK, Kim KH, Lee KS. Differential expression of pluripotent and germ cell markers in ovarian surface epithelium according to age in female mice. Reprod Biol Endocrinol. 2014;12:113.CrossRefPubMedPubMedCentral

27.

Bui HT, Van Thuan N, Kwon DN, Choi YJ, Kang MH, Han JW, et al. Identification and characterization of putative stem cells in the adult pig ovary. Development. 2014;141:2235–44.CrossRefPubMed

28.

Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, et al. A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4(+) stem cells identified in adult bone marrow. Leukemia. 2006;20:857–69.CrossRefPubMed

29.

Kucia M, Zuba-Surma E, Wysoczynski M, Dobrowolska H, Reca R, Ratajczak J, et al. Physiological and pathological consequences of identification of very small embryonic-like (VSEL) stem cells in adult bone marrow. J Physiol Pharmacol. 2006;57 Suppl 5:5–18.

30.

Kucia MJ, Wysoczynski M, Wu W, Zuba-Surma EK, Ratajczak J, Ratajczak MZ. Evidence that very small embryonic-like stem cells are mobilized into peripheral blood. Stem Cells. 2008;26:2083–92.CrossRefPubMed

31.

Kucia MJ, Halasa M, Wysoczynski M, Baskiewicz-Masiuk M, Moldenhawer S, Zuba-Surma E, et al. Morphological and molecular characterization of novel population of CXCR4+ SSEA-4+ Oct-4+ very small embryonic-like cells purified from human cord blood: preliminary report. Leukemia. 2007;21:297–303.CrossRefPubMed

32.

Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M. A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia. 2007;21:860–7.PubMed

33.

Shin DM, Liu R, Klich I, Wu W, Ratajczak J, Kucia M, et al. Molecular signature of adult bone marrow-purified very small embryonic-like stem cells supports their developmental epiblast/germ line origin. Leukemia. 2010;24:1450–61.CrossRefPubMed

34.

Mierzejewska K, Heo J, Kang JW, Kang H, Ratajczak J, Ratajczak MZ, et al. Genome-wide analysis of murine bone marrow-derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells. Int J Mol Med. 2013;32:281–90.PubMedPubMedCentral

35.

Shin DM, Liu R, Wu W, Waigel SJ, Zacharias W, Ratajczak MZ, et al. Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state. Stem Cells Dev. 2012;21:1639–52.CrossRefPubMedPubMedCentral

36.

Ratajczak MZ, Shin DM, Liu R, Marlicz W, Tarnowski M, Ratajczak J, et al. Epiblast/germ line hypothesis of cancer development revisited: lesson from the presence of Oct-4+ cells in adult tissues. Stem Cells Rev. 2010;6:307–16.CrossRef

37.

White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nature Med. 2012;18:413–21.CrossRefPubMedPubMedCentral

38.

Coffelt SB, Marini FC, Watson K, Zwezdaryk KJ, Dembinski JL, LaMarca HL, et al. The pro-inflammatory peptide LL-37 promotes ovarian tumor progression through recruitment of multipotent mesenchymal stromal cells. Proc Natl Acad Sci USA. 2009;106:3806–11.CrossRefPubMedPubMedCentral

39.

Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, et al. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PloS One. 2009;4:e4992.CrossRefPubMedPubMedCentral

40.

Kidd S, Spaeth E, Dembinski JL, Dietrich M, Watson K, Klopp A, et al. Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells. 2009;27:2614–23.CrossRefPubMedPubMedCentral

41.

McLean K, Gong Y, Choi Y, Deng N, Yang K, Bai S, et al. Human ovarian carcinoma-associated mesenchymal stem cells regulate cancer stem cells and tumorigenesis via altered BMP production. J Clin Invest. 2011;121:3206–19.CrossRefPubMedPubMedCentral

42.

Ricci F, Bernasconi S, Perego P, Ganzinelli M, Russo G, Bono F, et al. Ovarian carcinoma tumor-initiating cells have mesenchymal phenotype. Cell Cycle. 2012;11:1966–76.CrossRefPubMed

43.

Lis R, Touboul C, Raynaud CM, Malek JA, Suhre K, Mirshahi M, et al. Mesenchymal cell interaction with ovarian cancer cells triggers pro-metastatic properties. PLoS One. 2012;7:e38340.CrossRefPubMedPubMedCentral

44.

Waterman RS, Henkle SL, Betancourt AM. Mesenchymal stem cell 1 (MSC1)-based therapy attenuates tumor growth whereas MSC2-treatment promotes tumor growth and metastasis. PLoS One. 2012;7:e45590.CrossRefPubMedPubMedCentral

45.

Touboul C, Lis R, Al Farsi H, Raynaud CM, Warfa M, Althawadi H, et al. Mesenchymal stem cells enhance ovarian cancer cell infiltration through IL6 secretion in an amniochorionic membrane based 3D model. A J Transl Med. 2013;11:28.CrossRefPubMed

46.

Castells M, Milhas D, Gandy C, Thibault B, Rafii A, Delord JP, et al. Microenvironment mesenchymal cells protect ovarian cancer cell lines from apoptosis by inhibiting XIAP inactivation. Cell Death Dis. 2013;4:e887.CrossRefPubMedPubMedCentral

47.

Zhu P, Chen M, Wang L, Ning Y, Liang J, Zhang H, et al. Systemic mesenchymal stem cells reduce growth rate of cisplatin-resistant ovarian cancer. Int J Clin Exp Pathol. 2013;6:2506–14.PubMedPubMedCentral

48.

Lis R, Touboul C, Halabi NM, Madduri AS, Querleu D, Mezey J, et al. Mesenchymal cell interaction with ovarian cancer cells induces a background dependent pro-metastatic transcriptomic profile. J Transl Med. 2014;12:59.CrossRefPubMedPubMedCentral

49.

Touboul C, Vidal F, Pasquier J, Lis R, Rafii A. Role of mesenchymal cells in the natural history of ovarian cancer: a review. J Transl Med. 2014;12:271.CrossRefPubMedPubMedCentral

50.

Stimpfel M, Cerkovnik P, Novakovic S, Maver A, Virant-Klun I. Putative mesenchymal stem cells isolated from adult human ovaries. J Assist Reprod Genet. 2014;31:959–74.CrossRefPubMedPubMedCentral

51.

Kitagawa K, Murata A, Matsuura N, Tohya K, Takaichi S, Monden M, et al. Epithelial-mesenchymal transformation of a newly established cell line from ovarian adenosarcoma by transforming growth factor-beta1. Int J Cancer. 1996;66:91–7.CrossRefPubMed

52.

Ahmed N, Maines-Bandiera S, Quinn MA, Unger WG, Dedhar S, Auersperg N. Molecular pathways regulating EGF-induced epithelio-mesenchymal transition in human ovarian surface epithelium. Am J Physiol Cell Physiol. 2006;290:C1532–42.CrossRefPubMed

53.

Cao L, Shao M, Schilder J, Guise T, Mohammad KS, Matei D. Tissue transglutaminase links TGF-β, epithelial to mesenchymal transition and a stem cell phenotype in ovarian cancer. Oncogene. 2012;31:2521–34.CrossRefPubMed

54.

Jiang H, Lin X, Liu Y, Gong W, Ma X, Yu Y, et al. Transformation of epithelial ovarian cancer stemlike cells into mesenchymal lineage via EMT results in cellular heterogeneity and supports tumor engraftment. Mol Med. 2012;18:1197–208.CrossRefPubMedPubMedCentral

55.

Jiao J, Huang L, Ye F, Shi M, Cheng X, Wang X, et al. Cyclin D1 affects epithelial-mesenchymal transition in epithelial ovarian cancer stem cell-like cells. Onco Targets Ther. 2013;6:667–77.PubMedPubMedCentral

56.

Chen X, Zhang J, Zhang Z, Li H, Cheng W, Liu J. Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma. Hum Pathol. 2013;44:2373–84.CrossRefPubMedPubMedCentral

57.

Luo X, Dong Z, Chen Y, Yang L, Lai D. Enrichment of ovarian cancer stem-like cells is associated with epithelial to mesenchymal transition through an miRNA-activated AKT pathway. Cell Prolif. 2013;46:436–46.CrossRefPubMed

58.

Lam SS, Mak AS, Yam JW, Cheung AN, Ngan HY, Wong AS. Targeting estrogen-related receptor alpha inhibits epithelial-to-mesenchymal transition and stem cell properties of ovarian cancer cells. Mol Ther. 2014;22:743–51.CrossRefPubMedPubMedCentral

59.

Yan H, Sun Y. Evaluation of the mechanism of epithelial-mesenchymal transition in human ovarian cancer stem cells transfected with a WW domain-containing oxidoreductase gene. Oncol Lett. 2014;8:426–30.PubMedPubMedCentral

60.

Li Y, Gong W, Ma X, Sun X, Jiang H, Chen T. Smad7 maintains epithelial phenotype of ovarian cancer stem-like cells and supports tumor colonization by mesenchymal-epithelial transition. Mol Med Rep. 2015;11:309–16.PubMed

61.

Davidson B, Holth A, Hellesylt E, Tan TZ, Huang RY, Tropé C, et al. The clinical role of epithelial-mesenchymal transition and stem cell markers in advanced-stage ovarian serous carcinoma effusions. Hum Pathol. 2015;46:1–8.CrossRefPubMed

62.

Chiu WT, Huang YF, Tsai HY, Chen CC, Chang CH, Huang SC, et al. FOXM1 confers to epithelial-mesenchymal transition, stemness and chemoresistance in epithelial ovarian carcinoma cells. Oncotarget. 2015;6:2349–65.CrossRefPubMedPubMedCentral

63.

Ding YH, Zhou ZW, Ha CF, Zhang XY, Pan ST, He ZX, et al. Alisertib, an Aurora kinase A inhibitor, induces apoptosis and autophagy but inhibits epithelial to mesenchymal transition in human epithelial ovarian cancer cells. Drug Des Devel Ther. 2015;9:425–64.PubMedPubMedCentral

64.

Wang J, Chen D, He X, Zhang Y, Shi F, Wu D. Downregulated lincRNA HOTAIR expression in ovarian cancer stem cells decreases its tumorgeniesis and metastasis by inhibiting epithelial-mesenchymal transition. Cancer Cell Int. 2015;15:24.CrossRefPubMedPubMedCentral

65.

So KA, Min KJ, Hong JH, Lee JK. Interleukin-6 expression by interactions between gynecologic cancer cells and human mesenchymal stem cells promotes epithelial-mesenchymal transition. Int J Oncol. 2015;47:1451–9.PubMed

66.

Zhang J, Wang W, Qian L, Zhang Q, Lai D, Qi C. Ursolic acid inhibits the proliferation of human ovarian cancer stem-like cells through epithelial-mesenchymal transition. Oncol Rep. 2015;34:2375–84.PubMed

67.

Goyeneche AA, Koch M, Bell MC, Telleria CM. Long-term primary culture of a clear cell ovarian carcinoma reveals an epithelial-mesenchymal cooperative interaction. Cancer Cell Int. 2015;15:88.CrossRefPubMedPubMedCentral

68.

Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003;113:631–42.CrossRefPubMed

69.

Iv Santaliz-Ruiz LE, Xie X, Old M, Teknos TN, Pan Q. Emerging role of nanog in tumorigenesis and cancer stem cells. Int J Cancer. 2014;135:2741–8.CrossRefPubMed

70.

Kühn W, Kaufmann M, Feichter GE, Rummel HH, Schmid H, Heberling D. DNA flow cytometry, clinical and morphological parameters as prognostic factors for advanced malignant and borderline ovarian tumors. Gynecol Oncol. 1989;33:360–7.CrossRefPubMed

71.

Kiyozuka Y, Nakagawa H, Senzaki H, Uemura Y, Adachi S, Teramoto Y, et al. Bone morphogenetic protein-2 and type IV collagen expression in psammoma body forming ovarian cancer. Anticancer Res. 2001;21:1723–30.PubMed

72.

Giordano G, Gnetti L, Milione M, Piccolo D, Soliani P. Serous psammocarcinoma of the ovary: a case report and review of literature. Gynecol Oncol. 2005;96:259–62.CrossRefPubMed

73.

Zakkouri FA, Berrada N, Kettani F, Mrabti H, Jalil A, Errihani H. Aggressive ovarian psammocarcinoma: a case report. Eur J Gynaecol Oncol. 2011;32:214–5.PubMed

74.

Bergman RA, Afifi AK, Heidger PM. Blood. In: Atlas of Microscopic Anatomy.http://www.anatomyatlases.org/MicroscopicAnatomy/Section04/Section04.shtml. Accessed November 2015.

75.

Peracchio C, Alabiso O, Valente G, Isidoro C. Involvement of autophagy in ovarian cancer: a working hypothesis. J Ovarian Res. 2012;5:22.CrossRefPubMedPubMedCentral

76.

Virant-Klun I, Skutella T, Cvjeticanin B, Stimpfel M, Sinkovec J. Serous papillary adenocarcinoma possibly related to the presence of primitive oocyte-like cells in the adult ovarian surface epithelium: a case report. J Ovarian Res. 2011;4:13.CrossRefPubMedPubMedCentral

77.

Fereydouni B, Salinas-Riester G, Heistermann M, Dressel R, Lewerich L, Drummer C, et al. Long-Term Oocyte-Like Cell Development in Cultures Derived from Neonatal Marmoset Monkey Ovary. Stem Cells Int. 2016;2016:2480298.CrossRefPubMedPubMedCentral

78.

Hübner K, Kehler J, Schöler HR. Oocytes. Methods Enzymol. 2006;418:284–307.CrossRefPubMed

79.

Niu Z, Hu Y, Chu Z, Yu M, Bai Y, Wang L, et al. Germ-like cell differentiation from induced pluripotent stem cells (iPSCs). Cell Biochem Funct. 2013;31:12–9.CrossRefPubMed

Title: Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer
Authors: Irma Virant-Klun
Natasa Kenda-Suster
Spela Smrkolj
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Ovarian Research / Issue 1/2016
Electronic ISSN: 1757-2215
DOI: https://doi.org/10.1186/s13048-016-0221-3

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Small putative NANOG, SOX2, and SSEA-4-positive stem cells resembling very small embryonic-like stem cells in sections of ovarian tissue in patients with ovarian cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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