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. 2017 Sep 14;4(3):67. doi: 10.3390/medicines4030067

Table 1.

Membrane markers of esophageal cancer stem cells.

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.