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Feedback Forum > English Adult > Medical & Pharmaceutical > The Endothelin Axis

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    The Endothelin Axis

    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.

    Endothelins are peptides that exert their effects by binding via two G-protein coupled receptors, endothelin receptor A and B (ET-A and ET-B). ET-A and ET-B appear to promote tumor progression by several mechanisms, including cell proliferation, inhibition of apoptosis, angiogenesis, matrix remodeling, and bone deposition in skeletal metastases through activation of osteoblasts.

    Activation of ET-A by endothelin-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 vedge-F in response to hypoxia. ET-A activation also induces matrix-degrading enzymes, such as matrix metalloproteinases and urokinase plasminogen activator, which have important roles in tissue remodeling and tumor metastasis.

    In neuronal cells, ET-1/ET-A binding is involved in nociceptive effects associated with cancer bone metastasis and remodeling, and thus may be associated with the bone pain in patients with bone metastasis. In contrast, activation of ET-B by ET-1 promotes vasodilation and induces apoptosis in human cancer cells.

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