Table 2.: Selective Markers of Human Epithelial Stem Cells in Cervical Cancer

Sample CSCs Markers % Tumor Cells with CSCs Marker Min. CSCs to Engraft Recapitulation of Original Tumor Phenotype Serial Transplant Performed Additional Assays Ref.
Normal cervix and CIN I-II-III p63 CK17 * - - - - Martens, 2004 [32]
Normal cervix and CSCC Nanog
Normal cervix < 65% and CSCC > 90%, with all markers** - - - Correlation with clinicopathological features Ye, 2008 [39]
Normal cervix and CSCC PSCA
Normal cervix < 9% and CSCC > 50% - - - Correlation with clinicopathological features and HPV16 Liu, 2010 [40]
Normal cervix, CIN-III, CSCC, cell lines and spheres Sox2 SiHa and spheres from primary cancer tissues: positive. Normal cervix: 25%, CIN III: 83%, CSCC: 77% 106 SiHa-Sox2 cells Yes No Proliferation and clonogenicity of exogenous Sox2 in Hela and SiHa cell lines Ji, 2010 [42]
Invasive carcinomas and adenocarcinomas ALDH Invasive squamous carcinoma 25% and adenocarcinomas 20% - - - CD133 expression Yao, 2011 [45]
SiHa and Ca Ski cell lines Spheres
CaSki: 32%
SiHa: 0%
Ca Ski: 30%
- - - A431 sphere characterization Bortolomai, 2010 [46]
HeLa cell line Spheres
HeLa-Twist elevate the level of SFE, ALDH1 and CD44 in HeLa - - - Activation of -catenin and Akt pathways by Twist and suppression of CD44 expression by inhibition of signaling pathways. Li, 2011 [51]
CSCC Spheres - 105 Yes No Chemoresistance assay Expression of embryonic and stemness genes Feng, 2009 [52]
HeLa, SiHa, Ca Ski and C33A cell lines Spheres HeLa: 18% 104 - No Chemoresistance assay and gene silencing of E6 in HeLa sphere-forming cells Gu, 2011 [53]
HeLa, SiHa, Ca Ski and C-4I cell lines Spheres-CD49f 4-12% 103 Yes Yes Gene expression analysis and radioresistance assay López, 2012 [44]

Abbreviations: CSCs, Cancer stem cells; CIN, Cervical intraepithelial neoplasia; CK, Cytokeratin; CSCC, Cervical squamous cell carcinoma; PSCA, Prostate stem cell antigen; PIWIL1, Piwi-like protein 1; ALDH, Aldehyde dehydrogenase.
* In normal ectocervical epithelium, p63 was restricted to the basal compartment in 76-100% of cells in all cases and CK17, was in 26-50%. In endocervical epithelium, p63 and CK17 were not expressed. Subcolumnar reserve cells in the transitional zone and endocervix showed p63 and CK17 expression in 76-100% of cells in all cases. In CIN I and -II, the basal compartment showed p63 expression in 76-100% of cells in all cases. In CIN III lesions, staining was noted throughout the entire epithelial thickness. CK17 expression was noted in the basal compartment of all CIN lesions, irrespective of their grade, in 26-50% of cells in all cases.
** Expression >5%