Endothelin
The endothelin axis, which comprises endothelins and their receptors, is thought to have a role in the pathophysiology of tumors, including prostate, ovarian, colon, lung, breast, and kidney tumors.1 Endothelins are peptides that exert their effects by binding via 2 G-protein–coupled receptors—endothelin receptors A and B (ETA and ETB). ETA and ETB appear to regulate tumor progression by several mechanisms, including cell proliferation, inhibition of apoptosis, angiogenesis, matrix remodeling, and bone deposition in skeletal metastases through activation of osteoblasts.1-3
- Activation of ETA by endothelin-1 (ET-1) promotes tumor growth and progression by inhibiting apoptosis, synergizing with other growth factors to cause cell proliferation, and by stimulating the production of the key angiogenic factor VEGF in response to hypoxia2
- ETA activation also induces matrix-degrading enzymes, such as matrix metalloproteinases and urokinase plasminogen activator, which have important roles in tissue remodeling and tumor metastasis.3 In neuronal cells, ET-1/ETA binding is involved in nociceptive effects associated with cancer bone metastasis and remodeling, and thus may be associated with bone pain in patients with bone metastasis4
- In contrast, activation of ETB by ET-1 promotes vasodilation and induces apoptosis in human cancer cells.5 In addition, following activation of ETB, the endothelin-ETB complex is internalized, which in turn decreases the concentration of endothelin in the blood
The endothelin axis is thought to have a role in the tumor pathophysiology, including prostate, ovarian, colon, lung, breast, and kidney tumors. View how endothelin antagonism may impact cancer. Click the play button below.
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