AUTORADIOGRAPHIC LOCALIZATION OF ENDOTHELIN-1 BINDING-SITES IN HUMAN COLONIC-CANCER TISSUE

Endothelin-1, a potent vasoconstrictor, has been reported to stimulate mitogenesis in various types of normal and neoplastic cells and to be involved in neurotransmission. Recently, many human cancer cell lines, including those from the human colon, have been shown to produce endothelin. In this study, the occurrence of endothelin-1 binding sites was investigated in human colonic cancer tissues using in vitro autoradiography. Specific [I-125]endothelin-1 binding sites were identified over tumour vessels and stromal tissues surrounding cancer cell nests. The distribution was heterogeneous, and dense silver grains were localized, especially over clusters of fibroblasts adjacent to the cancer cell nests. Endothelin binding was minimal in the cancer cells, as in the normal crypt epithelium. Quantitative analysis of the autoradiographs demonstrated high affinity (K(d) = 0.50 +/- 0.06 nm; mean +/- SEM) binding sites, with a maximum binding capacity (B(max)) of 40 +/- 3.2 amol/mm2 in the cancer tissues. Our results provide evidence that specific endothelin-1 binding sites are expressed in the stromal tissues including tumour vessels, fibroblasts, and nerve fibres. Endothelin-1 may play a modulatory role in blood supply, mitogenesis, and neurotransmission in a paracrine fashion through the stromal components in human colonic cancers.