Differential expression of endothelin receptor subtypes in cancer

Objectives To explore the potential of tracers targeting the endothelin receptor as in vivo cancer imaging candidates, expression of both endothelin A and B receptor subtypes was quantified using a Beta-Imager in 65 surgically resected human tumor samples and matched normal tissues from kidney, brain, prostate, breast and lungs.

Methods Receptor subtype density in the 20-um thick tissue sections was evaluated using displacement receptor autoradiography (50 nM BQ-788 for subtype A and 50 nM BMS204970 for subtype B) with the universal endothelin receptor peptide 125I ET-1(20 pM). Pharmacologic competition experiments using 10 uM BMS204970 were performed to provide proof of specificity of the procedure.

Results Endothelin receptor subtype expression was found to be markedly different among human tumors examined. Increased expression of ETAR was more common in surgical specimens of prostate cancer (tumor/normal uptake ratio = 15.6±18.7), renal carcinoma (tumor/normal uptake ratio = 1.8±0.7) and glioblastoma(tumor/normal uptake ratio = 4.4±1.4) and less common in lung cancer(tumor/normal uptake ratio = 1.0±0.4). ETBR was overexpressed in primary breast carcinomas (tumor/normal uptake ratio = 9.0±13.7). In lung cancer both ETAR and ETBR were displayed, with the ETBR being the dominant subtype (tumor/normal uptake ratio = 2.0±1.2).

Conclusions The presented data indicate significant differences in the expression of endothelin receptors in different types of cancer and may help select patients suitable for in vivo imaging of the endothelin receptors in the future. High tumor-to background ratios on the basis of the high T/N receptor expression ratios are expected in prostate cancer and brain tumor (subtype A) and breast tumor (subtype B).

Research Support Supported by NIH grants: S10 RR022528; R21 CA115532; P50 CA103175. Dr. Gulaldi is a research fellow supported by the Turkish Scientific and Technical Research Council (TUBITAK).