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Table 1 Role of ET-1 and its receptors in different malignancies

From: Endothelin receptors as novel targets in tumor therapy

  Action of ET-1 Endothelin receptors Receptor antagonists and their effects
Prostate cancer ET-1 promotes prostate cancer growth, inhibits apoptosis through the ETAR High ETAR expression, decreased or absent ETBR expression, frequent methylation of ETBR gene Atrasentan relieves pain, and delays time to clinical and biochemical progression in prostate cancer patients
Ovarian cancer ET-1 promotes cell proliferation survival, invasion and VEGF-dependent angiogenesis through ETAR ETAR mRNA is detected in 84% carcinoma examinated, ETBR in only 40%. ETAR mediates all ET-1 induced tumor promoting effects Atrasentant inhibits cell proliferation and growth of ovarian carcinoma xenografts and displays additive effects in combination with taxanes
Melanoma ET-1 and ET-3 promotes melanoma cell proliferation and invasion ETAR are downregulated in melanoma cells. ETBR expression is increased in melanoma cells in comparison to benign nevi ETBR antagonist inhibits growth of melanoma cells lines, and reduces human melanoma tumor growth in nude mice.
Bone malignancies ET-1 increases osteocalcin expression and new bone formation Both ETAR and ETBR are expressed ETAR antagonist blocks ET-1-mediated effects and also inhibits progression of skeletal metastases in prostate cancer patients
Breast cancer Increased ET-1 expression inversely correlates with the degree of tumor cell differentiation Elevated expression of ETAR are detected in breast cancer tissue in comparison to normal  
Renal cancer ET-1 opposes the paclitaxel-induced apoptosis in renal carcinoma cell lines All cell lines express ETAR  
Lung cancer ET-1 is detected in most squamous cell and adenocarcinomas Both ETAR and ETBR are expressed; ETAR is downregulated in comparison to normal bronchial tissue  
Colon cancer ET-1 protects colon carcinoma cells from FasL-induced apoptosis Increased expression of ETAR and ETBR in neoplastic tissue ETA/BR antagonist, inhibits cell proliferation and potentiates FasL-induced apoptosis of tumor cells
Cervical cancer ET-1 induces proliferation of HPV-positive cervical carcinoma cell lines Express both ETAR and ETBR. Increased expression of ETAR on HPV-positive cells Atrasentan inhibits cell proliferation and growth of cervical carcinoma xenografts and displays additive effects in combination with taxane
Kaposi's ET-1 and ET-3 induces cell proliferation, migration and invasion Both ETAR and ETBR are expressed ETA,BR antagonist blocks ET-1 induced cell proliferation and invasion and inhibits tumor growth in nude mice
CNS tumors ET-1 promoted meningioma cell proliferation Both ETAR and ETBR are expressed BQ123 blocked ET-1-induced effects; ETAR antagonist had no effect