VIP Inhibits the Proliferation of Small-Cell and Nonsmall-Cell Lung Carcinoma

Maruno, Kaname; Said, Sami I.

doi:10.1111/j.1749-6632.1996.tb17499.x

Cited by 8 publications

(6 citation statements)

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“…However, PACAP was also found to inhibit proliferation of certain types of neuroblastoma cells and small cell lung cancer cells (45). PACAP inhibits cell proliferation through a cAMP-dependent pathway by the expression of its short variant, whereas the growth-stimulatory action of PACAP is via a PLC-dependent mechanism and via a MAPK pathway through the SV2 subtype of human PAC 1 -R (32,44,45). At least six human PAC 1 -R variants derived from alternative splicing have been reported in different tissues with seven putative membranespanning domains and belong to a family of glycoprotein receptors, which are coupled to multiple signal transduction pathways (38).…”

Section: Discussionmentioning

confidence: 99%

“…PACAP actions are most relevant to the proliferation or survival of tumor cells (44). However, PACAP was also found to inhibit proliferation of certain types of neuroblastoma cells and small cell lung cancer cells (45). PACAP inhibits cell proliferation through a cAMP-dependent pathway by the expression of its short variant, whereas the growth-stimulatory action of PACAP is via a PLC-dependent mechanism and via a MAPK pathway through the SV2 subtype of human PAC 1 -R (32,44,45).…”

Section: Discussionmentioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Cortez

Nakamachi

et al. 2006

Cancer Research

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Multiple myeloma represents a malignant proliferation of plasma cells in the bone marrow, which often overproduces immunoglobulin light chains. We have shown previously that pituitary adenylate cyclase-activating polypeptide (PACAP) markedly suppresses the release of proinflammatory cytokines from light chain-stimulated human renal proximal tubule epithelial cells and prevents the resulting tubule cell injury. In this study, we have shown that PACAP suppresses the proliferation of human K and L light chain-secreting multiple myeloma-derived cells. The addition of PACAP suppressed light chain-producing myeloma cell-stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor or the vasoactive intestinal peptide receptor attenuated the suppressive effect of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10 À9 mol/L PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen-activated protein kinases (MAPK) as well as nuclear factor-KB (NF-KB) activation in response to the adhesion of multiple myeloma cells to BMSCs, whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated paracrine stimulation of light chain-secreting myeloma cell growth was mediated through the suppression of p38 MAPK as well as modulation of activation of transcription factor NF-KB. These findings suggest that PACAP may be a new antitumor agent that directly suppresses light chain-secreting myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma. (Cancer Res 2006; 66(17): 8796-803)

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Cortez

Nakamachi

et al. 2006

Cancer Research

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“…In SCLS cell lines, VIP dose dependently inhibited cell proliferation. 33 Because VIP effects on cell proliferation were abolished by the PKA inhibitor KT5720, Maruno and Said 33 concluded that a cAMP/PKA pathway mediated the antiproliferative actions.PAC 1 -receptor variants derived from alternative splicing have been reported. Within the third intracellular loop, the insertion of 3 different cassettes called hip, hop1, and hop2 may generate 6 different variants called null (no insertion), hip, hop1, or hop2, and either hip-hop1 or hip-hop2 (2 cassettes).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Arimura

Batuman

2006

Blood

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The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end-stage kidney diseases. Myeloma kidney is associated with a significant increase in all-cause mortality, yet no effective intervention, except a limited use of steroid, is available. Here, we report that pituitary adenylate cyclaseactivating polypeptide with 38 residues (PACAP38) dramatically prevents injury of cultured renal proximal tubule cells caused by myeloma light chains through suppression of proinflammatory cytokines production, by inhibiting p38 MAPK and translocation of NFB via both PAC 1 and VPAC 1 receptors. The suppressive effects of PACAP was as effective as dexamethasone in all of their cytokine assays and demonstrated both in vitro and in vivo. Furthermore, PACAP38 inhibits myeloma cell growth directly and may also indirectly by suppressing production of the growth factor, IL-6, from bone marrow stromal cells, that is stimulated by adhesion of myeloma cells. These findings render PACAP38 worth evaluation as a promising candidate for an effective and safe renoprotectant in myeloma kidney, and possibly other nephropathy, and also as a new antitumor agent in multiple myeloma. ( IntroductionMultiple myeloma is the sixth most common cancer in the United States. About 13 200 new cases of multiple myeloma were diagnosed in 2000. According to the US Renal Data System, renal morbidity from multiple myeloma is substantial. 1 Myeloma kidney disease was associated with 250% increase in all-cause mortality. 1 The kidney is vulnerable to pathogenic effects of monoclonal light chains in multiple myeloma and other disease associated with overproduction of immunoglobulin light chains. The most common type of renal injury in multiple myeloma is chronic tubulointerstitial nephropathy associated with casts in tubule lumens, an entity referred to as "myeloma kidney" that often progresses to end-stage kidney disease. 2,3 Although the mechanisms of cast formation have been clarified in studies that showed that certain types of light chains behave as ligand binding to defined sites on Tamm-Horsfall proteins, 4 the mechanisms responsible for chronic tubulointerstitial injury have only recently been explored. 5,6 These studies showed that increased endocytosis and overloading by myeloma light chains in proximal tubule cells produce inflammatory cytokines. These cytokine responses were mediated by activation of nuclear factor NFB and signaled through MAPKs, ERK1/2, JNK, and p38 MAPK. Despite improved understanding of the pathophysiology, no effective treatment is known for myeloma kidney except for a limited use of steroids.Pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38) was isolated from ovine hypothalamic tissues based on the ability to stimulate adenylate cyclase in pituitary cell cultures. 7 PACAP38 is a new member of the vasoactive intestinal peptide (VIP) family of peptides. It is...

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“…A potential novel therapeutic agent for bladder cancer is vasoactive intestinal peptide (VIP), which is a 28-amino acid peptide that has multiple therapeutic actions, including bronchodilatory and anti-inflammatory properties ( 3 , 4 ). VIP inhibits the proliferation of small-cell lung cancer in vitro and in vivo in mice ( 5 ) and has been shown to upregulate nuclear expression of p53 in mouse renal cell carcinomas ( 6 ). Loss of expression of p53, a tumor suppressor, and its analogs leads to tumor growth and can also be found in patients with bladder cancer ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Mortality to Metastatic Bladder Cancer Cell Line MB49 in Vasoactive Intestinal Peptide Gene Knockout Mice

Mirsaidi

Burns

McClain³

et al. 2017

Front. Endocrinol.

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To identify if the absence of the vasoactive intestinal peptide (VIP) gene enhances susceptibility to death from metastatic bladder cancer, two strains of mice were injected with MB49 murine bladder cancer cells. The growth and spread of the cancer was measured over a period of 4 weeks in C57BL/6 mice and 5 weeks in VIP knockout (KO) mice. A Kaplan–Meier plot was constructed to compare control C57BL/6 mice and C57BL/6 mice with MB49 vs. VIP KO controls and VIP KO mice with MB49. The wild-type (WT) strain (C57BL/6) contained the VIP gene, while the other strain, VIP knockout backcrossed to C57BL/6 (VIP KO) did not and was thus unable to endogenously produce VIP. VIP KO mice had increased mortality compared to C57BL/6 mice at 4 weeks. The number of ulcers between both groups was not statistically significant. In vitro studies indicated that the presence VIP in high doses reduced MB49 cell growth, as well as macrophage inhibitory factor (MIF), a growth factor in bladder cancer cells. These findings support the concept that VIP may attenuate susceptibility to death from bladder cancer, and that it exerts its effect via downregulation of MIF.

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VIP Inhibits the Proliferation of Small-Cell and Nonsmall-Cell Lung Carcinoma

Cited by 8 publications

References 1 publication

Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells

Potential protective action of pituitary adenylate cyclase-activating polypeptide (PACAP38) on in vitro and in vivo models of myeloma kidney injury

Enhanced Mortality to Metastatic Bladder Cancer Cell Line MB49 in Vasoactive Intestinal Peptide Gene Knockout Mice

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