Table 1.
Marker | Function | Biological properties | Assays | Subpopulations | Clinical Significance |
---|---|---|---|---|---|
ABCG2 (ATP-Binding Cassette sub-family G member 2) |
This membrane protein functions as a xenobiotic transporter and may have a role in multi drug resistance. | Tumor spheres isolated fromEC cell lines are enriched in ABCG2+ cells. Cigarette smoke condensate induces ABCG2 expression and potentiates CSC properties. |
ABCG2+ cells isolated from EC cell lines and EC biopsies form tumor-spheres in vitro and tumors in vivo in nude mice. | ABCG2+/ALDH1+ cells are tumorigenic. | ABCG2 is overexpressed in ESCC, in association with tumor grade, stage and metastasis. 5-FU treatment increases ABCG2+ cells; 5-FU+COX2 inhibitor decreases ABCG2+ cells. |
CD44 Also, known as HCAM (Homing Cell Adhesion Molecule) |
CD44 is a cell surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. | CD44+/CD24- cells isolated from EC cell lines and EC biopsies have phenotypic and functional properties of CSCs. | CD44+/CD24- cells isolated from EC cell lines and EC biopsies form tumor-spheres in vitro and tumors in vivo in nude mice. | CD44+/CD24- cells have high sphere-forming potential, are resistant to irradiation, reside in hypoxic niches, formed tumors in xenotransplantation assays and their number correlated with tumor grade. CD44+/ICAM1+, CD44+/ALDH1+ and CD44+CD133+ have high CSC potential. |
The number of CD44+/CD24- cells correlated with response of residual EAC to chemo/radiation. CD44 expression increases during the progression of Barrett’s metaplasia to EAC. |
CD90 Also, known as Thy-1 |
CD90 is a heavily glycosylated, glyco- Psphatidylinositol anchored cell surface protein. CD90 is used as a marker for a variety of stem cell populations. |
CD90+ cells isolated from cancer cell lines have CSC properties. CD90 expression is increased in esophageal tumor tissues, compared to normal ones. |
CD90+ cells isolated from KYSE140 or KYSE520 cell lines form tumor-spheres in vitro and tumors in vivo in nude mice. | Only a minority of CD90+ cells co-express CD271 or CD44. | CD90 expression is upregulated in primary ESCC cells. 2–10% CD90+ cells in ESCCs. CD90+ cells are radio-resistant. |
CD133 Also, known as Promin-1 |
CD133 is a membrane glycoprotein, encoded by the PROM1 gene, member of the pentasman transmembrane glycoproteins. | CD133+ or CD133+/CXCR4+ cells isolated from EC cell lines and EC biopsies have phenotypic and functional properties of CSCs. | CD133+/CXCR4+ cells isolated from TE-1 cell line have a high colony-forming capacity. | CD133+/CXCR4+ cells have CSC properties with high proliferative potential. | CD133 expression associated with lymph node metastasis, clinical stage and histo- pathological grade. 21% of ESCCs have high CD133+/CXCR4 expression, associated with negative prognosis. CD133 expression increases during the progression of Barrett’s metaplasia to EAC. |
CD271 Also, known as p75 Neutrophin Receptor (p75NTR) |
CD271 is the low-affinity nerve growth factor receptor, one of the two receptor types for neutrophins. | CD271+ cells isolated from cancer cell lines (KYSE70) have CSC properties. | CD271+ cells isolated from EC cell lines and EC biopsies form tumor-spheres in vitro and tumors in vivo in nude mice. | CD271+/CD90+, CD271+/CD44+ cells have the same CSC function, compared to CD271+/CD90- , CD271+/CD44- cells. Quiescent CD271+ cells express ABCG2 and are chemoresistant. |
CD271 expression is higher in ESCC tissue than in normal esophageal epithelium. High CD271 expression is observed in 34% of ESCCs. |
ITGA7 (Integrin alpha 7) |
ITGA7 is a member of the integrin family of cell surface proteins that mediate cellular interactions with the extracellular matrix. Together with a beta subunit, it forms the functional receptor that binds laminin. | ITGA7+ cells isolated from cancer cell lines have CSC properties. ITGA7 overexpression pro- Motes CSC properties, metastasis and EMT. ITGA7 knockdown decreases CSC properties. |
in vitro: tumor-sphere In vivo: xenotranspanta- tion in nude mice. |
ITGA7 and CD90 are co-expressed. ITGA7+/CD90+ cells have a high clono- genic potential. |
ITGA7 expression is associated with poor prognosis in ESCC, poor differentiation and lymph node metastasis. Chemotherapy enriches ITGA7+ cells. |