The role of endothelin in colorectal cancer

Background: The vasoactive peptide endothelin-1 (ET-1) acts via two receptors, ETA and ETB. ET-1 is overexpressed by human colorectal cancer tissue. The aim was to elucidate whether 1) there is differential expression of ETA and ETB receptors in colorectal cancer and 2) ET-1 is a mitogenic factor for colorectal cancer. Method: The distribution of receptors in normal colon and in tissue from patients with colorectal cancer was determined by immunohistochemistry and by autoradiography. In vitro experiments with colorectal cancer cell lines were carried out to determine the presence of ETA and ETB in these cells using autoradiography, the effect of exogenous ET-1 on their growth and if ETA and ETB antagonists could modulate the ET-1 induced growth. Results: ETA is overexpressed in colorectal cancer as compared to normal colon while ETB is underexpressed. The density of expression of ETA in colorectal cancer significantly exceeded that of ETB. Both receptors were expressed by epithelial, and endothelial cells in normal colon and colorectal cancer. Neuronal normal colonic tissue also expressed both receptors. ET-1 acted as a growth stimulator for colorectal cancer cells and this effect was inhibited by ETA, but not by ETB, antagonists. Conclusion: ETA receptors are overexpressed in colorectal cancer. ET-1 can stimulate the proliferation of colorectal cancer cell lines via the ETA, but not the ETB, receptor