Reporter gene systems for the identification and characterization of cancer stem cells

Table 2 Studies using reporter system based on CSCs transcription factors.

Promoter gene/element response	Reporter gene	Tumor type	Functional assays performed for validation
NANOG	GFP; Luminescent protein	Breast cancer[100]	Sphere formation
			Limiting-dilution xenotransplantation
			Extravasation potential
			In vitro limiting-dilution assays
		Breast cancer[98]	Transactivation assay
		Prostate cancer[70]	Sphere formation
			Extravasation potential
			Drug sensitivity in vitro
			Limiting-dilution xenotransplantation
		Nasopharynx cancer [101]	Sphere formation
			Limiting-dilution xenotransplantation
			Extravasation potential
			Drug sensitivity in vivo
			Drug sensitivity in vitro
		Liver (hepatocellular carcinoma)[45]	Sphere formationLimiting-dilution xenotransplantation
			Extravasation potential
			Drug sensitivity in vitro
		Ovary cancer[89]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Ovary cancer[72]	Sphere formation
			Xenotransplantation assay
			Drug sensitivity in vitro
			Extravasation potential
SOX2	tdTomato fluorescent protein/ Luminescent protein; GFP; Luminescent protein	Breast cancer[17]	Sphere formation
		Breast cancer[102]	Sphere formation
		Breast cancer[43]	Sphere formation
			Drug sensitivity in vitro
			Transactivation assay
		Breast cancer[98]	Transactivation assay
		Glioma[46]	Sphere formation
			Xenotransplantation assay
			In vitro limiting-dilution assays
		Skin cancer[103]	Limiting-dilution xenotransplantation
			Drug sensitivity in vivo
		Cervical cancer[104]	Sphere formation
			Limiting-dilution xenotransplantation
		Cervical cancer[105]	Sphere formation
			Transactivation assay
		Thyroid cancer[106]	Transactivation assay
		Teratomas from neoplastic hPSCs[12]	Transactivation assay
			Drug sensitivity in vivo
			Progenitor assays (clonogenic and multilineage hematopoietic differentiation)
OCT4	GFP; Luminescent protein	Liver (hepatocellular carcinoma)[47]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Melanoma[92]	Sphere formation
			Drug sensitivity in vitro
			Xenotransplantation assay
		Sarcoma[18]	Xenotransplantation assay
			Drug sensitivity in vitro
			Drug sensitivity in vivo
		Breast cancer[43]	Sphere formation
			Drug sensitivity in vitro
			Transactivation assay
		Teratomas from neoplastic hPSCs[12]	Transactivation assay
			Drug sensitivity in vitro
			Progenitor assays (clonogenic and multilineage hematopoietic differentiation)
SOX2-OCT4	GFP; mCherry fluorescent protein; Luminescent protein; Luminescent protein/ RFP	Breast cancer[38]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Sarcoma[42]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Prostate cancer[107]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vivo
			Drug sensitivity in vitro
		Gastric cancer[44]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Malignant mesothelioma[108]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Head and neck squamous cancer[109]	Sphere formation
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
		Glioma[16]	Sphere formation
			Transactivation assay
			Limiting-dilution xenotransplantation
			Drug sensitivity in vitro
			Drug sensitivity in vivo

hPSCs: Human pluripotent stem cells; GFP: Green fluorescent protein; RFP: Red fluorescent protein