Stem Cells International

Review Article

Cancer Stem Cells: From an Insight into the Basics to Recent Advances and Therapeutic Targeting

Table 4

Markers used for identification of CSCs in tumors [19].


Cancer type	Markers for CSCs	Molecular weight (kDa)	Chromosomal location (in human)	Description of the markers	References

Acute myeloid leukemia	CD10⁺	100	3q25.2	Inhibits peptide hormones like glucagon, bradykinin, and oxytocin.	[31]
	CD19⁺	95	16p11.2	Involved in class of molecules of signal transduction and regulates differentiation of B-lymphocyte.	[32]
	CD20⁺	33-37	11q12.2	Helps in the development of plasma cells from the differentiated B cells.	[33]
	CD34⁺	105-120	1q32.2	Helps in the attachment of stem cells to bone marrow.	[34]
	CD38^-	42	4p15.32	Acts as an intracellular messenger for Ca²⁺ mobilization and also acts as a prognostic marker for patients suffering from chronic lymphocytic leukemia.	[19]
	CD44⁺	85-250	11p13	Cell surface protein when targeted leads to the eradication of leukemic stem cells.	[35]
	CD45RA⁺	205-220	1q31.3-q32.1	Acts as a class of activation regulators for leukocytes.	[36]
	CD71⁺	190	3q29	Acts as a transferrin receptor essential for the development of nerve.	[37]
	CD123⁺	70	Xp22.3 and Yp13.3	Acts as an interleukin-specific subunit of the cytokine receptor which is heterodimeric.	[38]

Brain cancer	A2B5⁺	—	—	Acts as a monoclonal antibody specific of polysialogangliosides and to a lesser extent of polysialoproteins. It helps to identify the subpopulations of nerve cells in the CNS.	[19]
	CD36⁺	85	7q21.11	Acts as the main glycoprotein, is present on the surface of platelet, and functions as an adhesion molecule.	[39]
	CD44⁺	85-220	11p13	Acts as a glycoprotein, which gets knockdown in glioblastoma xenograft models resulting in the inhibition of cell growth and improved response to chemotherapy.	[40]
	CD49f⁺	125	2q31.1	Acts as a subunit of the family of laminin receptors, which has been used to detect TICs.	[41]
	CD90⁺	25-35	11q23.3	Acts as a glycoprotein that is required for T cell adhesion and signal transduction.	[19]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres, produces tumors in vivo, and exhibits the property of chemoresistance.	[42]
	EGFR⁺	170-180	7p11.2	Promotes proliferative migration in the tumors by binding to the epidermal growth factor.	[43]
	L1CAM⁺	200-220	Xq28	Acts as an adhesion molecule and is important for development, neuronal migration, and differentiation of the nervous system.	[19]

Breast cancer	ALDH⁺	54	9q21.13	Acts as an enzyme responsible for providing resistance to cell.	[44]
	CD44⁺/CD24^-	85-250/35-45	11p13/6q21	Glycoprotein plays a role in the process of cellular migration and self-renewal. During metastasis, it increases blood flow in the tumor.	[45]
	CD49f⁺	125	2q31.1	Acts as a protein of the integrin family, which is present on the membrane and is responsible for signaling and cell surface adhesion.	[19]
	CD90⁺	25-35	11q23.3	Acts as a glycoprotein that is required for T cell adhesion and signal transduction.	[19]
	CD133⁺	115-125	4p15.32	Lipid composition in the cell membranes is maintained by this transmembrane glycoprotein.	[46]
	CD44⁺	85-250	11p13	Monitors variations in ECM and therefore influences cell growth, survival, and differentiation.	[47]
	CD44v6⁺	85-250	11p13	Is responsible for cellular migration and adhesion.	[48]

Cervical cancer	ABCG2⁺	72	4q22.1	Is among the largest families of transmembrane proteins that is implicated in providing resistance to camptothecin analogues and mitoxantrone.	[49]
	ALDH⁺	54	9q21.13	Marker possesses the ability to self-renew and differentiate and has enhanced tumorigenicity.	[46]
	CD49f⁺	125	2q31.1	In the presence of this marker, the cells can self-renew, enhance tumorigenic capabilities, and increase resistance to ionizing radiation.	[49]
	CD133⁺	115-125	4p15.32	Acts as a glycoprotein having 5 transmembrane domains that help in detecting the tumor.	[49]
	CD44⁺	85-250	11p13	Acts as a marker that causes tumor invasiveness and metastasis.	[50]
	CD49f⁺	125	2q31.1	Acts as a subunit of the family of laminin receptors, which has been used to detect TICs.	[41]
	CD133⁺	115-125	4p15.32	Acts as a biomarker that plays a role in cell-cell and cell-matrix contact formation.	[51]
	CD166⁺	100-105	3q13.11	Binds to CD6 which is a T cell differentiation antigen and plays a role in cell adhesion and migration.	[19]
	CD200⁺	45-50	3q13.2	Acts as a glycoprotein which is regulating immunosuppression and antitumor activity.	[19]
	CD206⁺	162-175	10p12.33	Acts as a mannose receptor that plays a major role in endocytosis, phagocytosis, and immune homeostasis	[52]
	EpCAM⁺	40	2p21	Acts as an homotypic cell adhesion molecule which is calcium-independent and can be expressed on normal epithelial cells and gastrointestinal cancers.	[53]

Cutaneous squamous-cell carcinoma (cSCC)	CD44⁺	85-250	11p13	Acts as a putative tumor cell surface marker with increased concentration in subpopulation of SCC.	[54]
Cutaneous squamous-cell carcinoma (cSCC)	CD133⁺	115-125	4p15.32	Transmembrane glycoprotein and its upregulation play an important role in tumorigenic processes and development of CSCs.	[55]

Esophageal cancer	ALDH⁺	54	9q21.13	Acts as an intracellular enzyme that helps in detoxifying aldehydes and regulating the conversion of retinoic acid from retinol.	[56]
	CD44⁺	85-250	11p13	Receptor that acts as an activator for the tyrosine kinase receptor, thus increases tumor cell proliferation via MAPK.	[56]
	CD90⁺	25-35	11q23.3	Acts as a surface glycoprotein whose expression can lead to tumor heterogeneity and malignancy.	[19]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres, gives rise to tumors in vivo, and exhibits chemoresistance properties.	[42]

Gall bladder cancer	CD44⁺/CD133⁺	85-250/115-125	11p13/4p15.32	Act as the potential markers of CSCs and detect their expression in primary GBC as well as in the GBC-SD cell line.	[57]

Head and neck squamous cell carcinoma	ALDH⁺	54	9q21.13	Acts as an intracellular enzyme that refines for cancer stem cells and involved in EMT.	[13]
	CD44⁺	85-250	11p13	Acts as a cell-surface glycoprotein, acts as a receptor for hyaluronic acid, and is involved in the process of cell adhesion and migration associated with tumor progression and metastatic spread of HNSCC.	[13]
	CD133⁺	115-125	4p15.32	Transmembrane glycoprotein and cells possessing this glycoprotein found to have high clonogenicity, invasiveness, and tumorigenicity and are also resistant to paclitaxel.	[13]

Laryngeal cancer	ALDH⁺	54	9q21.13	Intracellular enzyme and cells using it as a biomarker possess increased potential to proliferate.	[58]
	CD44⁺	85-250	11p13	Acts as a cell surface glycoprotein whose overexpression signifies the aggressiveness and a prognostic factor in LC.	[58]
	CD133⁺	115-125	4p15.32	Acts as a putative CSC marker and is also identified in the human laryngeal tumor Hep-2 cell line as a marker of CSCs.	[58]

Liver cancer	CD13⁺	150-170	15q26.1	Acts as a receptor of human coronavirus strain, causing infection in upper respiratory tract and leukemia.	[59]
	CD24⁺	35-45	6q21	Acts as a marker that during metastasis, it increases blood flow in the tumor.	[60]
	CD44⁺	85-250	11p13	Acts as a glycoprotein that plays a role in the process of cellular migration and self-renewal.	[61]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres, produces tumors in vivo, and exhibits chemoresistance properties.	[42]
	CD206⁺	162-175	10p12.33	Acts as a biomarker that can predict the progression of liver cancer.	[52]
	EpCAM⁺	40	2p21	Regulates EMT, stemness, and metastasis of cells via the PTEN/AKT/mTOR pathway.	[62]
	OV-6⁺	—	—	Acts as a mouse monoclonal antibody raised against isolated hepatic oval cells. It acts as a marker for oval cells in rat and hepatic stem cells.	[19]
	CD44⁺	85-250	11p13	Acts as a transmembrane glycoprotein that is involved in various processes like invasion, migration, and adhesion.	[63]
	CD87⁺	32-56	19q13	Acts as a receptor used to activate urokinase plasminogen and affecting many normal and pathological processes which are associated with plasminogen activation of the cell surface and local degradation of extracellular matrices.	[19]
	CD90⁺	25-35	11q23.3	Surface molecular marker of CSCs and cells possessing this marker have higher proliferation, self-renewal, and tumorigenic capacity.	[64]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres, produces tumors in vivo, and exhibits chemoresistance properties.	[41]
	CD166⁺	100-105	3q13.11	Expressed on the cell surface by interacting with the tumor cells via heterotypically or homotypically.	[65]

Malignant mesothelioma	CD9⁺	24	12p13.31	Acts as a glycoprotein responsible for differentiation, adhesion, and signal transduction in normal cell and movement and metastasis in cancer cell.	[66]
	CD24⁺	35-45	6q21	Acts as a marker which is present on the cells and leads to proliferation via an asymmetric cell division-like manner.	[67]
	CD26⁺	110	2q24.2	Acts as an intrinsic membrane-bound glycoprotein and a member of serine exopeptidase family.	[67]

Melanoma	ALDH⁺	54	9q21.13	Intracellular enzyme and those cells using it as a biomarker possess increased potential to proliferate.	[68]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres and generates tumors in vivo and possesses chemoresistance properties.	[69]
	CD271⁺	45	17q21.33	Acts as a receptor for nerve growth factor and mediates cell proliferation and nerve cell death.	[70]
	CD27⁺	50-55	12p13.31	Acts as a transmembrane glycoprotein that controls B cell activation and the production of immunoglobulins.	[71]
	CD138^-	92	2p24.1	Is a part of the syndecan proteoglycan family that involves in cell proliferation and differentiation and association between cells and matrices.	[72]

Nasopharyngeal cancer	ALDH⁺	54	9q21.13	Intracellular enzyme and those cells using it as a biomarker possess increased potential to proliferate.	[73]
	EpCAM⁺	40	2p21	Regulates EMT, stemness, and metastasis of cells via the PTEN/AKT/mTOR pathway.	[62]
	CD44⁺	85-250	11p13	Monitors variations in ECM and therefore influences cell growth, survival, and differentiation.	[74]
	CD133⁺	115-125	4p15.32	Glycoprotein is expressed in many tumor cells lines.	[75]

Oral squamous cell carcinoma (OSCC)	CD44⁺/CD24^-	85-250/35-45	11p13/6q21	Receptor used for hyaluronic acid and it acts as an activator for the tyrosine kinase receptor, thus increases proliferation of tumor cells via MAPK.	[76]
Oral squamous cell carcinoma (OSCC)	ITGA7⁺	128.9	12q13.2	Acts as an integrin responsible for metastasis, cell migration, morphogenesis, and differentiation, and during the process of myogenesis, it plays a role in differentiation and migration.	[77]

Ovarian cancer	ALDH⁺	54	9q21.13	Only a detectable marker was expressed in all primary tumors.	[78]
	CD24⁺	35-45	6q21	Acts as a biomarker which defines an ovarian cancer-initiating cell population.	[79]
	CD44⁺/CD117⁺	85-250/	11p13	Acts as a class of transmembrane receptors classified as stem cell factors.	[19]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres and generates tumors in vivo and possesses chemoresistant properties.	[19]

Pancreatic cancer	ABCG2⁺	72	4q22.1	Acts as a membrane protein which is a part of ABC transporters and involves in the drug-resistant properties of CSCs.	[80]
	ALDH⁺	54	9q21.13	Is associated with the tumorigenic cells present in the pancreatic ductal adenocarcinoma.	[80]
	CD44⁺/CD24⁺/EpCAM⁺	85-250/35-45/40	11p13/6q21/2p21	Acts as a biomarker present on the cells which possesses the ability to form tumors.	[19]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that forms spheres and generates tumors in vivo and possesses chemoresistant properties.	[42]
	CXCR4⁺	40	2q22.1	Is associated with the patient’s prognosis having pancreatic tumors and can be used for targeting tumors.	[81]

Prostate cancer	α2β1⁺	160	5q11.2	Acts as a receptor required for cell adhesion and recognition.	[82]
	ALDH⁺	54	9q21.13	Acts as an enzyme whose increased activity can be used for isolating human prostate cancer cells with enhanced properties of clonogenesis and migration in vitro as well as increased tumor- and metastasis-initiating capacity in vivo.	[83]
	CD44⁺	85-250	11p13	Acts as a receptor used for hyaluronic acid, and it acts as an activator for the tyrosine kinase receptor, thus increases proliferation of tumor cells via MAPK.	[84]
	CD166⁺	100-105	3q13.11	Acts as a surface marker used for enrichment of both murine and human prostate tissue stem or progenitor cells on the basis of in vitro sphere formation and in vivo tissue regeneration.	[85]
	CD133⁺	115-125	4p15.32	Acts as a cell surface marker used to identify CSCs in prostate cancer cell lines.	[86]
	CXCR4⁺	40	2q22.1	Acts as a receptor for CXC chemokine function with CD4 protein to facilitate the entry of HIV into cells.	[19]
	E-cadherin⁺	75-80	16q22.1	Acts as a key permissive factor that enables in vitro invasion of cancer stem cell.	[87]
	EZH2⁺	43.5	7q36.1	Acts as a member of polycomb family which is essential in the CNS.	[19]

Renal cell carcinoma (RCC)	ALDH⁺	54	9q21.13	Acts as a biomarker that promotes formation of sphere, clonogenicity, proliferation, and invasion of the cells.	[42]
	CD44⁺	85-250	11p13	Promotes various signaling pathways including activation of MAPK, PI3K/AKT, RTK, and TGFβ, via supporting cellular proliferation, survival, and invasion.	[42]
	CD105⁺	90	9q34.11	Acts as a receptor present in the TGF-β signaling and is responsible for angiogenesis.	[19]
	CD133⁺	115-125	4p15.32	Acts as a transmembrane glycoprotein that produces spheres by giving rise to tumors in vivo and possessing chemo-resistant properties.	[42]
	CXCR4⁺	40	2q22.1	Acts as a G protein-coupled receptor (GPCR) with the seven transmembranes on the cell membrane known to be part of cell-stroma interactions leading to a permissive niche for metastasis.	[42]

Stomach cancer	ALDH⁺	54	12q24.12	Acts as a marker that generates chemoresistance via the Notch1 and Shh signaling.	[88]
	CD24⁺	35-45	6q21	Acts as a cell surface protein that acts as a ligand for P-selectin, which is expressed on the cell surfaces of activated platelets and endothelial cells, in the process of tumor dissemination.	[89]
	CD44⁺	85-250	11p13	Cell surface receptor plays a crucial role in degradation of matrix, proliferation, and cell survival.	[19]
	CD44v8-10⁺	85-250	11p13	Is derived from CD44 having a specific class of CSCs.	[19]
	CD49f⁺	125	2q31.1	Acts as a subunit of the family of laminin receptors, which has been used for identifying TICs.	[41]
	CD54⁺	75-115	19p13.2	Acts as an adhesion molecule expressing in tumor cells which are malignant.	[19]
	CD71⁺	190	3q29	Acts as a transferrin receptor acting as a carrier protein that transports iron within the cell and helps in maintaining the cellular iron homeostasis.	[90]
	CD90⁺	25-35	11q23.3	Acts as a membrane GPI-anchored protein.	[91]
	CD133⁺	155-125	4p15.32	A marker when present in CSCs exhibits self-renewal potential and tumor formation.	[86]