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 Musashi-1 Nucleostemin |
Normal cervix < 65% and CSCC > 90%, with all markers** | - | - | - | Correlation with clinicopathological features | Ye, 2008 [39] |
| Normal cervix and CSCC | PSCA PIWIL1 TBX2 |
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 ALDH |
CaSki: 32% SiHa: 0% Ca Ski: 30% SiHa:24% |
- | - | - | A431 sphere characterization | Bortolomai, 2010 [46] |
| HeLa cell line | Spheres ALDH1 CD44 |
HeLa-Twist elevate the level of SFE, ALDH1 and CD44 in HeLa | - | - | - | Activation of β-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%