We report that BBS stimulates COX-2 mRNA and protein expression, and the release of prostaglandin E2 from the GRP receptor (GRPR)-positive, androgen-insensitive prostate cancer cell line, PC-3.
Both agents bound Ace-1(huGRPr) and PC-3, a known GRPr-expressing human prostate cancer cell line, with 4-13 nM IC50 against (125) I-Tyr(4) -BBN, but did not bind Ace-1(CMV) cells (vector transfected).Binding was blocked by bombesin.
In the present study, we developed an (18)F-labeled bombesin analog, (18)F-BAY 86-4367, which is currently being clinically tested for use in PET of prostate cancer.
Prostate cancer cells usually express both PSMA and gastrin-releasing peptide (GRP) receptors; thus, bispecific heterodimeric molecules, addressing both targets at the same time, may significantly improve prostate cancer imaging and therapy.
The detection of a wide distribution of bombesin/GRP receptors in human prostate carcinomas supports the view that they may be involved in modulation of tumor progression and suggests that approaches based on binding of bombesin receptor antagonists or new targeted cytotoxic bombesin analogs to prostate cancers could be considered for the therapy.
Evaluation of a ⁶⁴Cu‑labeled 1,4,7‑triazacyclononane, 1‑glutaric acid‑4,7 acetic acid (NODAGA)‑galactose‑bombesin analogue as a PET imaging probe in a gastrin‑releasing peptide receptor‑expressing prostate cancer xenograft model.
Taken together, these data suggest that BN acts as a mitogen in prostate cancer and this might be associated with the activation of the transcription factor Elk-1 and the immediate early gene c-fos.
Importantly, GRP is a key neuroendocrine peptide, which may be involved in the progression of advanced prostate cancer and in the neuroendocrine differentiation of prostate cancer.
We investigated the effects of GHRH antagonists MZ-J-7-118 and RC-J-29-18, BN/GRP antagonists RC-3940-II and RC-3940-Et and the combination of MZ-J-7-118 and RC-3940-II on the growth of PC-3 and DU-145 human androgen independent prostate cancers xenografted s.c. into nude mice.
Bombesin (BN) and gastrin-releasing peptide (GRP) have been shown to stimulate the growth of human prostate cancer in vivo and in vitro by mechanisms initiated by binding of the peptide to BN/GRP receptor (GRPR).
Recently, elastin-like polypeptide (ELP)-based self-assembling micelles with tethered GRP on the surface have been suggested to actively target prostate cancer cells.
Prostate cancer cell receptors that play a role in these processes include the gastrin-releasing peptide (GRP) receptor, neurotensin receptors, and the epidermal growth-factor receptor (EGFR).
In view of the involvement of various neuropeptides and growth factors in the progression of androgen-independent prostate cancer, we investigated the effects of antagonists of growth hormone-releasing hormone (GHRH) alone or in combination with an antagonist of bombesin/gastrin-releasing peptide (BN/GRP) on PC-3 human prostate cancers.
<sup>68</sup>Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC).
NEP normally functions to inactivate peptides such as bombesin and endothelin-1, and potentiates the effects of the PTEN tumor suppressor via a direct protein-protein interaction.NEP loss contributes to PC progression.
A previous study showed GRPR-mediated binding of radiolabeled BN analogs in androgen-dependent but not in androgen-independent xenografts representing the more advanced stages of PC.
Despite still investigational, the bombesin-based radiotracers and antagonist of gastrin releasing-peptide receptor (GRP) (RM2) and anti1-amino-3-18Ffluorocyclobutane-1-carboxylic acid (18F-FACBC) are emerging as possible alternatives for investigating PCa.
LH-RH antagonist Cetrorelix (SB-75) and the BN/GRP antagonist RC-3940-II were tested for their effects on the growth of the androgen-independent PC-3 human prostate cancer cell line xenografted into nude mice.
Bombesin, a peptide of 14 amino acids, is an amphibian homolog to the mammalian gastrin-releasing peptide (GRP), that has been extensively studied as a targeting ligand for diagnosis and therapy of GRP positive tumors, such as breast, pancreas, lungs and prostate cancers.
Different bombesin analogs have been radiolabeled and used for imaging diagnosis, staging, evaluation of biochemical recurrence, and assessment of metastatic disease in patients with prostate cancer.
Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC).