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

BackgroundIn 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.MethodsIn 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.ResultsIn 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0221-3) contains supplementary material, which is available to authorized users.

Ovarian Cancer Stem Cells: Unraveling a Germline Connection

“…Similarly, NANOG + cells/structures with unknown biological and clinical significance were also reported within BL ovarian cortex Primary antibody was detected by secondary antibody conjugated with Alexa fluor 488, and tissue sections were counterstained with nucleus specific dye DAPI. Color images available online at www.liebertpub.com/scd region by same group [39]. In another similar study same authors investigated pluripotency (OCT4, SOX2, NANOG, and SSEA4) and germinal lineage (VASA/DDX4 and DPPA3/ STELLA) related markers in tiny spherical cells (5 mm) found in close vicinity of borderline ovarian tumor cell cultures.…”

Verrucarin J inhibits ovarian cancer and targets cancer stem cells

“…As reported above, VJ targets ALDH1 + cells. To validate that VJ targets other CSC populations in addition to ALDH1 + CSC population, we examined the effect of VJ on expression of genes for NANOG, LGR5 and OCT4, reported to be present in ovarian cancer [ 12 , 13 , 30 – 34 ]. LGR5 (leucine rich-repeat G protein-coupled receptor 5) has been shown to maintain adult intestinal stem cells, postembryonic development, and is expressed in ovarian cancer [ 30 , 31 , 34 ].…”

“…In ovarian cancer, the most common CSCs identified include CD24, CD34, CD44, CD117, ALDH1, EpCAM, SSEA4, NANOG, MYD88, and SOX2 positive cells [ 13 ]. ALDH1 + represents as one of the major populations in ovarian cancer [ 12 ]. Increased number of CSCs in ovarian tumors correlate with poor prognosis, including shorter overall life [ 18 , 19 ].…”

Do Somatic Cells De-differentiate/Trans-differentiate or VSELs Initiate Cancer and Explain Plasticity in Adult Tissues?

“…Virant-Klun's group is leading the field to show that similar VSELs observed in normal ovary are also visualized in ovarian cancer samples. Small round cells (2-4 mm) expressing NANOG, SOX2 and SSEA4 were detected in surface epithelium of ovarian cancer samples [72]. VSELs in ovary surface epithelium are best candidates that could undergo malignant transformation into CSCs [73].…”