Neurotensin Receptor-1 Expression in Human Prostate Cancer: A Pilot Study on Primary Tumors and Lymph Node Metastases

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.

The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review

“…A more recent study, studying the NTSR1 expression in normal, benign prostatic hyperplasia (BPH), prostatic cancer and metastatic lymph nodes, there was no clear association between NTSR1 and age, PSA values, Gleason score, pathological T stage, but there was more frequent NTSR1 overexpression in metastatic lymph nodes compared to primary tumours (p = 0.038) [49]. The authors concluded, in this study, that this may open a new perspective in imaging and radionuclide therapy in prostate cancer [49].…”

Key-Protease Inhibition Regimens Promote Tumor Targeting of Neurotensin Radioligands

“…Accordingly, the neurotensin subtype 1 receptor (NTS1R) [7,8] has been regarded as an attractive molecular target for such purposes owing to its high density expression in many human cancers [9,10]. Thus, high NTS1R expression has been documented in pancreatic ductal adenocarcinoma [11][12][13], Ewing's sarcoma [14], colon carcinoma [15], prostate [16] and breast cancer [17], as well as other cancer types [18]. This finding offers the opportunity to develop theranostic NTS1R-directed radioligands based on the native tridecapeptide neurotensin (NT) for oncological applications.…”

Optimizing the Profile of [99mTc]Tc–NT(7–13) Tracers in Pancreatic Cancer Models by Means of Protease Inhibitors

“…The neurotensin subtype 1 receptor (NTS1R) has been regarded as a valid biomolecular target in cancer theranostics, owing to its high-density expression in a variety of human tumors, such as pancreatic ductal adenocarcinoma (PDAC), colon carcinoma, Ewing's sarcoma, or prostate and breast cancer [1][2][3][4][5][6][7][8][9][10][11][12]. This overexpression can be elegantly exploited to direct NTS1R-seeking radionuclide carriers to tumor sites [13,14].…”

“…This overexpression can be elegantly exploited to direct NTS1R-seeking radionuclide carriers to tumor sites [13,14]. Typically, radiolabeled analogs of the C-terminal hexapeptide fragment of neurotensin (NT = Pyr-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH), NT (8)(9)(10)(11)(12)(13), have been considered for such purposes [15][16][17][18][19][20][21][22][23][24]. For stable binding of metal radionuclides, a suitable Int.…”

“…We have previously developed a small library of NT (7)(8)(9)(10)(11)(12)(13) analogs, coupled to an acyclic tetraamine chelator at the N-terminus for stable binding of the eminent SPECT radionuclide [ 99m Tc]Tc. The preclinical evaluation of this series of compounds was carried out in human colon adenocarcinoma HT29 and WiDr cells expressing the NTS1R [28,29].…”