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 | Â |
Renal cancer | ET-1 opposes the paclitaxel-induced apoptosis in renal carcinoma cell lines | All cell lines express ETAR | Â |
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 | Â |
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 |