Bombesin stimulates growth of human prostatic cancer cellsin vitro

Bologna, Mauro; Festuccia, Claudio; Muzi, Paola; Biordi, Leda; Ciomei, Marina

doi:10.1002/1097-0142(19900501)63:9<1714::aid-cncr2820630912>3.0.co;2-h

Cited by 205 publications

(114 citation statements)

References 21 publications

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“…2 It has been shown that the receptor for bombesin/GRP was expressed in prostate cancer cell lines and that the proliferation of PC-3 prostate cancer cells was significantly enhanced by bombesin in vitro. 18,19 Bombesin was also observed to increase the invasive capacity of PC-3 prostate cancer cells, 4 and stimulated the secretion of MMP-9 and an increase of urokinase-type plasminogen activator (u-PA) activity. 20 Our previous and present studies have demonstrated that GRP enhanced the invasion of both PC-3 and DU-145 cells to Matrigel and the haptotactic migration of PC-3, DU-145, TSU-pr1 and LNCaP cells to fibronectin, but it had no effect on either the gelatinolytic activities of MMP-9 or fibrinolytic activities of u-PA in fibrin zymography of PC-3 and DU-145 cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Effect of prostatic neuropeptides on migration of prostate cancer cell lines

et al. 2001

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Background: A previous study by the same authors demonstrated that among various neuropeptides in the prostate, calcitonin gene-related peptide (CGRP) and gastrin-releasing peptide (GRP) increased the invasive capacity of PC-3 prostate cancer cells through enhancement of cell motility, while substance P (SP) inhibited the invasiveness through suppression of motile response. Methods:The effect of 10 kinds of neuropeptides were investigated, including CGRP, GRP, SP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucineenkephalin (L-ENK), methionine-enkephalin (M-ENK), glucagon and parathyroid hormone-related protein (PTH-rP), on the invasion of DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel) and the haptotactic migration of DU-145, TSU-pr1 and LNCaP prostate cancer cells using a Transwell cell culture chamber assay. Results: It was found that GRP, CGRP and PTH-rP increased the invasive capacity of tumor cells. In contrast, SP, VIP, CT, L-ENK, M-ENK, NPY and glucagon had no significant effect. These three neuropeptides also increased the haptotactic migration of tumor cells to fibronectin. In addition VIP, CGRP and GRP increased the haptotactic migration of LNCaP prostate cancer cells and GRP and PTH-rP increased the migration of TSU-pr1 cells. Conclusion:The results indicated that some prostatic neuropeptides increased the invasive potential of prostate cancer cells partially through enhancement of cell motility.

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Section: Discussionmentioning

confidence: 99%

Effect of prostatic neuropeptides on migration of prostate cancer cell lines

et al. 2001

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“…Bombesin and calcitonin each exert a proliferative effect on the androgen-independent PC-3 and DU-145 prostate cancer cell lines (Bologna et al, 1989;Jongsma et al, 2000;Larran et al, 2000), as well as stimulation of PC3 cell migration (Aprikian et al, 1997). Cell growth and DNA synthesis are increased when prostate cancer cells are stimulated with PTHrP (Iwamura et al, 1994;Tovar-Sepulveda and Falzon, 2002).…”

Section: Introductionmentioning

confidence: 99%

Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src/Stat5b pathway

2006

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Neuroendocrine (NE)-like cells are hypothesized to contribute to the progression of prostate cancer by producing factors that enhance the growth, survival or metastatic capabilities of surrounding tumor cells. Many of the factors known to be secreted by NE-like cells, such as neurotensin (NT), parathyroid hormone-related peptide, serotonin, bombesin, etc., are agonists for G-proteincoupled receptors, but the signaling pathways activated by these agonists in prostate tumor cells are not fully defined. Identification of such pathways could provide insights into novel methods of treating late-stage disease. Using conditioned culture medium (CM) from LNCaPderived NE-like cells (as a source of these agonists) or NT (a prototypical component of CM) to treat PC3 cells, we found that the epidermal growth factor (EGF) receptor (EGFR) was transactivated and that such activation was required for maximal PC3 cell mitogenesis, as measured by 5-bromo-2 0 -deoxy-uridine incorporation or cell number. NT also induced a time-dependent increase in EGFR Tyr 845 phosphorylation and phosphorylation of c-Src and signal transducer and activator of transcription 5b (Stat5b) (a downstream effector of Tyr 845 ), events that were blocked by specific inhibition of c-Src (which mediates Tyr 845 phosphorylation of EGFR) or of EGFR. Introduction of mutant forms of EGFR (Tyr 845 ) or Stat5b in PC3 cells, or treatment with selective, catalytic inhibitors of EGFR, c-Src and matrix metalloproteinases (MMPs) resulted in the loss of NT-induced stimulation of DNA synthesis, relative to wild-type controls. These data indicate that the mitogenic effect of NT on prostate cancer cells requires transactivation of the EGFR by MMPs and a novel downstream pathway involving c-Src, phosphorylation of EGFR Tyr 845 and activation of Stat5b.

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“…Clinical and preclinical data have indicated a mitogenic role for small regulatory peptides such as endothelin-1 (ET-1), bradykinin, bombesin-like peptides and neurotensin in various stages of prostate cancer (Bologna et al, 1989;Papandreou et al, 1998). Endothelin-1, in particular, has been demonstrated in prostatic tissue in vivo and in human PC lines in vitro with plasma ET-1 concentrations significantly elevated in men with metastatic disease (Nelson et al, 1995).…”

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Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

et al. 2004

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Perturbations of stromal -epithelial interactions in the developing tumour can contribute to cancer invasion and metastasis. The structurally related metallopeptidases endothelin-converting enzyme (ECE) and neutral endopeptidase (NEP) contribute sequentially to the synthesis and inactivation of ET-1, a mitogenic peptide that has been shown to affect tumour behaviour. This study has investigated the interaction between metastatic tumour epithelial cells, which lack NEP, and stromal cells, which we have shown to express ECE-1 (stromal -epithelial interactions), using Matrigel invasion chambers. The epithelial cell lines utilised in this study include androgen-sensitive LNCaP, androgen-independent PC-3, Du145 and recently established PNT-1a, PNT2-C2 and P4E6 prostate cell lines. Specific inhibition of endogenous ECE-1 activity in stromal cells reduced PC-3 and Du145 invasion by 70 and 50%, respectively. Addition of recombinant NEP to inactivate endogenous mitogenic peptides resulted in 50 and 20% reductions in invasion in PC-3 and Du145 cells, respectively. Neutral endopeptidase effects were reversed in the presence of thiorphan, a specific NEP inhibitor. Supplementation of defined media with bradykinin and ET-1 significantly increased PC-3 invasion by 40 and 50%, respectively. Du145 cell invasion increased by approximately 100% on adding ET-1. These studies implicate the metallopeptidases NEP and ECE-1 as mediators of prostate cancer invasion via a stromal/epithelial interaction.

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Bombesin stimulates growth of human prostatic cancer cellsin vitro

Cited by 205 publications

References 21 publications

Effect of prostatic neuropeptides on migration of prostate cancer cell lines

Effect of prostatic neuropeptides on migration of prostate cancer cell lines

Neurotensin stimulates mitogenesis of prostate cancer cells through a novel c-Src/Stat5b pathway

Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

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