Endothelin binding studies in human primary non-small cell lung cancers

Abstract

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Endothelins (ET−1, −2, −3) are 21-amino acid peptides expressed and released from numerous cell types such as endothelial cells, epithelial cells, macrophages and fibroblasts. ETs also exhibit pro-mitogenic, angiogenic and anti-apoptotic properties suggesting their participation in tumor growth and development. The gene expression profile of seven endothelin-related genes in human primary non-small cell lung cancers showed that the ET system is present in the vast majority of human NSCLC tumors, supporting a role for ETs in the physiology of this type of cancer. Here, we continued our investigation into conducting binding studies for the two receptor subtypes (ETA-R, ETB-R) using the same human lung biopsies from those NSCLC: squamous carcinoma (SQ; n=6), bronchioloalveolar carcinoma (BAC; n=6), large cell carcinoma (LC; n=6) or adenocarcinoma (AD; n=6) as well as from normal controls (n=5). Using RT-PCR, we previously detected the expression ETA-R and ETB-R in all non-tumoral (NT) and tumoral (T) lung tissues. ETB-R mRNA expression were significantly lower in SQ tumors compared to other NSCLC types. The % of ETA-R subtype was significantly elevated in SCC compared to NT. The % of ETB-R subtype rather significantly decreased in ADB, SCC and LCC, but not in ADK, vs NT. Interestingly, total ET-R density was doubled in the NT tissue of lung cancer patients vs. controls. This was true for both the A and B subtypes of the ET-R. However, in the T lung tissue, the density of both ET-R subtypes was decreased (75%) compared to the PT tissue. Compared to the controls, with the exception of LCC, the density of ET-R was lower (40%) in T lung tissues. The density of ETB-R decreased in all tumor types whereas ETA-R density remain stable, except in ADK where it decreased. Conclusion: Presence of a lung tumor has great influence on the both ET-A and ET-B receptors density. In fact, the expression of ET-R is greatly increased in the PT tissue while it is decreased in the tumor proper. The implication of this on lung tumor physiology remains obscure.