Bombesin specifically induces intracellular calcium mobilization via gastrin-releasing peptide receptors in human prostate cancer cells

Aprikian, A.; Han, Kwan Hee; Chevalier, Simone; Bazinet, Michel; Viallet, Jean

doi:10.1677/jme.0.0160297

Cited by 68 publications

(81 citation statements)

References 23 publications

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“…These neuroendocrine cells express a variety of bioactive neuropeptides including GRP. A number of studies document the elevated expression of GRP receptors in prostate cancer specimens (Bartholdi et al, 1998;Markwalder and Reubi, 1999;Sun et al, 2000a) and on cultured prostatic cancer cell lines (Aprikian et al, 1996), supporting a paracrine role for GRP in prostate cancer progression.…”

Section: Bombesin-like Peptidesmentioning

confidence: 97%

Autocrine and paracrine signaling through neuropeptide receptors in human cancer

2001

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Autocrine and paracrine signaling leading to stimulation of tumor cell growth is a common theme in human cancers. In addition to polypeptide growth factors such as EGF family members which signal through receptor tyrosine kinases, accumulating evidence supports the autocrine and paracrine involvement of speci®c neuropeptides with de®ned physiologic actions as neurotransmitters and gut hormones in lung, gastric, colorectal, pancreatic and prostatic cancers. These neuropeptides, including gastrin-releasing peptide, neuromedin B, neurotensin, gastrin, cholecystokinin and arginine vasopressin bind seven transmembrane-spanning receptors that couple to heterotrimeric G proteins. Studies with human small cell lung cancer (SCLC) cells support a requirement for balanced signaling through G q and G 12/13 proteins leading to intracellular Ca 2+ mobilization, PKC activation and regulation of the ERK and JNK MAP kinase pathways. While speci®c neuropeptide antagonists o er promise for interrupting the single neuropeptide autocrine systems operating in pancreatic and prostatic cancers, SCLC is exempli®ed by multiple, redundant neuropeptide autocrine systems such that tumor growth cannot be inhibited with a single speci®c antagonist. However, a novel class of neuropeptide derivatives based on the substance P sequence have been de®ned that exhibit broad speci®city for neuropeptide receptors and induce apoptosis in SCLC by functioning as biased agonists that stimulate discordant signal transduction. Thus, interruption of autocrine and paracrine neuropeptide signaling with speci®c antagonists or broad-spectrum biased agonists o er promising new therapeutic approaches to the treatment of human cancers. Oncogene (2001) 20, 1563 ± 1569.

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Section: Bombesin-like Peptidesmentioning

confidence: 97%

Autocrine and paracrine signaling through neuropeptide receptors in human cancer

2001

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“…Proliferation and DNA synthesis of PC3 cells (Seethalakshmi et al, 1997;Lee et al, 2001;Hassan and Carraway, 2006), and also of LNCaP cells in the absence of androgen (Sehgal et al, 1994;Lee et al, 2001), are stimulated when cells are treated with NT. Receptors for bombesin (Reile et al, 1994;Aprikian et al, 1996;Xiao et al, 2002), NT (Seethalakshmi et al, 1997;Dal Farra et al, 2001;Petit et al, 2001) and PTHrP (Tovar-Sepulveda and Falzon, 2002) are expressed by PC3, LNCaP and/or DU145 prostate cancer cells and have been characterized with respect to proliferative function. Thus, mitogenic neuropeptides that are secreted by NE-like cells can activate specific membrane-bound receptors on the surface of prostate cancer cells, resulting in increased proliferation and DNA synthesis.…”

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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“…Receptors for these ligands have also been localized within the prostate epithelium (Reubi, 1995;Wu et al, 1996;Killam et al, 1995;Gup et al, 1990;Lepor and Kuhar, 1984;Abdul et al, 1994;Carmena et al, 1995;Aprikian et al, 1996). Their mitogenic in¯uence on the neighboring cells is documented by the ®ndings that prostate cells in the vicinity of NE cells display increased expression of Bcl-2 and Ki-67 antigens (Segal et al, 1994;van Weerden et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Constitutive activation of stimulatory guanine nucleotide binding protein (GSαQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells

et al. 1999

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Bombesin specifically induces intracellular calcium mobilization via gastrin-releasing peptide receptors in human prostate cancer cells

Cited by 68 publications

References 23 publications

Autocrine and paracrine signaling through neuropeptide receptors in human cancer

Autocrine and paracrine signaling through neuropeptide receptors in human cancer

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

Constitutive activation of stimulatory guanine nucleotide binding protein (GSαQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells

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