Abstract
Neurotensin and its high-affinity receptor, NTR1, are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and 15 related metastatic lymph nodes (one per patient, when available). NTR1-staining was negative in normal prostate and BPH samples. NTR1 was overexpressed in four out of 44 (9.1%) primary tumors. There was no clear association between NTR1 overexpression and age, PSA-values, Gleason score, pT-status, nodal-status, or margin. NTR1 was expressed at a high level of five out of 15 (33.3%) metastatic lymph nodes. NTR1 overexpression was thus more frequent in metastatic lymph nodes than in primary tumors (p = 0.038). In this limited series of samples, NTR1 overexpression was observed in few primary prostate cancers. Upregulation was more frequent in related lymph nodes. The presence of this target in metastatic lymph nodes may open new perspectives for imaging and radionuclide therapy of prostate cancer. Factors driving NTR1 expression in primary prostate cancer and in nodal and distant metastases still need to be characterized.
Highlights
Prostate cancer is the most frequent cancer in men
Expression of NTR1 at the mRNA level does not necessarily translate into similar results at the protein levels [12,13]. In light of these conflicting results and given the paucity of data on human prostate cancer samples, we investigated in this pilot study NTR1 expression in samples of normal human prostate tissues, benign prostatic hyperplasia (BPH), primary prostate cancer, and metastatic lymph nodes
Immunocytochemistry results revealed that formalin-fixed PC-3 cells express NTR1, whereas formalin-fixed LNCaP cells exhibit weak NTR1 expression
Summary
Prostate cancer is the most frequent cancer in men. It is initially an androgen-dependent disease that may progress to an androgen-independent stage: castration resistant prostate cancer (CRPC) with poor prognosis related to the reactivation of androgen-receptor (AR) transcriptional activity [1,2]. After binding to its high-affinity receptor, NTR1, neurotensin stimulates mitosis of cancerous prostatic cells through Src-, MMP-, and PKC-dependent ligand-mediated transactivation of EGFR, which mediate IGF-1R phosphorylation and stimulation of the MAP kinase pathway in a PI3K-dependent manner [5,6,7]. The selective NTR1 antagonist SR48692 is able to inhibit the neurotensin-induced growth of prostate cancer cells [6], suggesting the involvement of NTR1 as an oncogenic receptor in prostate cancer. Androgen deprivation induces acute neurotensin production, suggesting the involvement of neurotensin and its receptors in androgen-independent prostate cancer and/or neuroendocrine differentiation of prostate cancer [8,9,10]. To assess the potential applications of neurotensin receptors, NTR1 expression has been analyzed in several prostate cancer cell models with controversial results. Expression of NTR1 at the mRNA level does not necessarily translate into similar results at the protein levels [12,13]
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