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

Prostate cancer

ET-1 promotes prostate cancer growth, inhibits apoptosis through the ET_AR

High ET_AR expression, decreased or absent ET_BR expression, frequent methylation of ET_BR 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 ET_AR

ET_AR mRNA is detected in 84% carcinoma examinated, ET_BR in only 40%. ET_AR 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

ET_AR are downregulated in melanoma cells. ET_BR expression is increased in melanoma cells in comparison to benign nevi

ET_BR 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 ET_AR and ET_BR are expressed

ET_AR 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 ET_AR 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 ET_AR

Lung cancer

ET-1 is detected in most squamous cell and adenocarcinomas

Both ET_AR and ET_BR are expressed; ET_AR is downregulated in comparison to normal bronchial tissue

Colon cancer

ET-1 protects colon carcinoma cells from FasL-induced apoptosis

Increased expression of ET_AR and ET_BR in neoplastic tissue

ET_A/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 ET_AR and ET_BR. Increased expression of ET_AR 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 ET_AR and ET_BR are expressed

ET_A,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 ET_AR and ET_BR are expressed

BQ123 blocked ET-1-induced effects; ET_AR antagonist had no effect