Cancer stem cells (CSCs) have been identified in solid human cancers, including breast, colon, and ovary. Recent evidence suggests that the highly regenerative human endometrium harbors rare populations of epithelial stem/progenitor cells1. We hypothesised that CSCs are responsible for the epithelial neoplasia associated with endometrial carcinoma (EC), the most common gynaecological malignancy in women. The aim of this study was to demonstrate that a rare population of EC cells posses CSC properties. Stem cell characteristics were assessed in 25 EC and 2 endometrial hyperplasia tissues obtained from women aged 62 ± 9 yrs. Samples were cultured at clonal densities (100–500 cells/cm2) for 3–5 wks to determine cloning efficiency. Individual clones were serially subcloned (<10 cells/cm2) every 2–4 wks to determine self renewal capacity. Isolated cells in serial dilution (103–106 cells) were placed under the kidney capsule of immunocompromised mice for 12–16 wks to examine for the presence of tumour initiating cells (TIC). Resulting tumours and original parent tumours were examined for markers by immunohistochemistry. Most samples (23/26) contained rare colony forming cells. The cloning efficiency was 0.23% ± 0.28% (n = 11) in G1, 0.78% ± 0.67% (n = 8) in G2, 0.22% ± 0.21% (n = 3) in G3, 0.03% (n = 2) in type II tumours, and 0.14% (n = 2) in hyperplasia samples, and did not differ significantly between grades or between type I EC and normal endometrial epithelial samples 1. Single cell derived clones subcloned 2.5 ± 1.4 (n = 11), 3.2 ± 0.4 (n = 5), 3.5 (n = 2), 3.0 ± 1.7 (n = 3), and 2.5 (n = 2) times in G1, G2, G3, type II tumours and hyperplasia samples respectively, indicating increasing self renewal capacity with increasing tumour grade. Transplanted EC single cell suspensions initiated tumour growth with similar morphology, ERα, PR, EpCAM, cytokeratin, and vimentin expression as the parent tumour, indicating the presence of TIC. This evidence suggests that rare cells possessing the CSC properties of clonogenicty, self renewal, and tumorigenicity, may be responsible for the initiation and progression of EC.
(1) Chan RWS et al. (2004). Biology of Reproduction. 70:1738–1750
Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells