Neurotensin Receptor Expression in Human Adeno- and Squamous Cell Carcinoma

There is increasing interest in targeting peptide receptors and their ligands for tumor diagnostics and therapy since there is evidence that various of these receptors are overexpressed in tumors compared to their expression in normal tissues. Among these receptors playing a key role in tumor progression is the neurotensin receptor (NTR) family. The present study investigated the expression of NTR in HT29 cells (human colon adenocarcinoma), in FaDu cells (human squamous cell carcinoma), and in the corresponding HT-29 and FaDu xenografts in nude mice as a well characterized animal tumor model. Quantitative RT-PCR with specific primers for the three NTR subtypes was done to study mRNA expression. Receptor protein expression was analysed by in vitro autoradiography using [³H]neurotensin(8-13) and by immunohistochemistry with specific antibodies against the three neurotensin receptors NTR1, NTR2, and NTR3. Analysis of receptor mRNA revealed a strong expression of NTR3 and a weaker expression of NTR1 and NTR2. Looking at protein levels, strong signals for NTR1 and NTR2 (NTR1 > NTR2) were detected immunohistochemically both in tumor cells and the corresponding xenografts. In contrast, expression of NTR3 revealed only a very weak immunopositive staining in tumors. Because it is the receptor protein that is targeted in vivo, the enhanced expression of NTR1 and NTR2 in these tumor entities could be a useful target for diagnostics, e.g., with radioligands suitable for single photon or positron emission tomography.