https://doi.org/10.4081/ejh.2024.3994
Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report
Submitted: 19 February 2024
Accepted: 19 March 2024
Published: 2 May 2024
Accepted: 19 March 2024
Abstract Views: 930
PDF: 249
HTML: 8
HTML: 8
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Pleural mesothelioma is a devastating malignancy primarily associated with asbestos exposure. However, emerging evidence suggests that exposure to fluoro-edenite fibers, a naturally occurring mineral fiber, can also lead to the development of pleural mesothelioma. In this study, based on the hypothesis that pituitary adenylate cyclase-activating polypeptide (PACAP) and PACAP-preferring receptor (PAC1R) expressions could be dysregulated in pleural mesothelioma samples and that they could potentially act as diagnostic or prognostic biomarkers, we aimed to investigate the immunohistochemical expression of PACAP and PAC1R in pleural biopsies from patients with pleural mesothelioma exposed to fluoro-edenite fibers. A total of 12 patients were included in this study, and their biopsies were processed for immunohistochemical analysis to evaluate the expression of PACAP and its receptor. The study revealed a correlation between the overexpression of PACAP and PAC1R and shorter overall survival in patients with malignant mesothelioma. These findings suggest that PACAP and PAC1R expression levels could serve as potential prognostic biomarkers for malignant mesothelioma. Furthermore, the immunohistochemical analysis of PACAP and PAC1R may provide valuable information for clinicians to guide therapeutic decisions and identify patients with poorer prognosis.
Downloads
Download data is not yet available.
Publication Facts
Metric
This article
Other articles
Peer reviewers
1
2.4
Reviewer profiles N/A
Author statements
Author statements
This article
Other articles
Data availability
N/A
16%
External funding
N/A
32%
Competing interests
N/A
11%
Metric
This journal
Other journals
Articles accepted
57%
33%
Days to publication
72
145
- Editor & editorial board
- profiles
- Academic society
- N/A
- Publisher
- PAGEPress Publications, Pavia, Italy
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
Citations
Robinson BW, Musk AW, Lake RA. Malignant mesothelioma. Lancet 2005;366:397-408.
DOI: https://doi.org/10.1016/S0140-6736(05)67025-0
Barone AD, Mastrantonio M, Romeo L. Environmental risk factors in pleural malignant mesothelioma. Medicina Lavoro 2012;103:29-42.
Ledda C, Loreto C, Lombardo C, Cardile V, Rapisarda V. Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers. Transl Oncol 2024;40:101872.
DOI: https://doi.org/10.1016/j.tranon.2023.101872
Comba P, Gianfagna A, Paoletti L. Pleural mesothelioma cases in Biancavilla are related to a new fluoro-edenite fibrous amphibole. Arch Environ Occup H 2011;66:70-6.
Magnani C, Dalmasso P, Biggeri A. Increased risk of malignant mesothelioma of the pleura after residential or domestic exposure to asbestos: a case-control study in Casale Monferrato, Italy. Environ Health Perspect 1996;104:1208-13.
Fazz L, Minelli G, De Santis M. Pleural mesothelioma mortality and asbestos exposure mapping in Italy. Am J Ind Med 2015;58:1224-34.
Grosse Y, Loomis D, Guyton KZ, Lauby-Secretan B, El Ghissassi F, Bouvard V, et al. Carcinogenicity of fluoro-edenite, silicon carbide fibres and whiskers, and carbon nanotubes. Lancet Oncol 2014;15:1427-8.
DOI: https://doi.org/10.1016/S1470-2045(14)71109-X
Ballan G, Del Brocco A, Loizzo S, Fabbri A, Maroccia Z, Fiorentini C, Travaglione S. Mode of action of fibrous amphiboles: the case of Biancavilla (Sicily, Italy). Ann Ist Super Sanita 2014;50:133-8.
Filetti V, Vitale E, Broggi G, Hagnäs MP, Candido S, Spina A, et al. Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review. Biomed Rep 2020;13:60.
DOI: https://doi.org/10.3892/br.2020.1367
Loreto C, Caltabiano R, Graziano ACE, Castorina S, Lombardo C, Filetti V et al. Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1. Eur J Histochem 2020;64:3073.
DOI: https://doi.org/10.4081/ejh.2020.3073
Filetti V, Loreto C, Falzone L, Lombardo C, Cannizzaro E, Castorina S, et al. Diagnostic and prognostic value of three microRNAs in environmental asbestiform fibers-associated malignant mesothelioma J Pers Med 2021;15;11:1205.
DOI: https://doi.org/10.3390/jpm11111205
Sayan M, Mossman BT. The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases. Part Fibre Toxicol 2016;13:51.
DOI: https://doi.org/10.1186/s12989-016-0162-4
Lombardo C, Broggi G, Vitale E, Ledda C, Loreto C, Matera S, et al. Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report. Histol Histopathol 2023;38:1249-56.
Filetti V, Lombardo C, Loreto C, Dounias G, Bracci M, Matera S, et al. Small RNA-Seq transcriptome profiling of mesothelial and mesothelioma cell lines revealed microRNA dysregulation after exposure to asbestos-like fibers. Biomedicines 2023;11:538.
DOI: https://doi.org/10.3390/biomedicines11020538
Ledda C, Lombardo C, Tendi EA, Hagnas M, Paravizzini G, Filetti V, et al. Pathway of inflammation due to asbestiform fiber “fluoro-edenite” exposure: an update. Curr Respir Med Rev 2020;16:73-5.
DOI: https://doi.org/10.2174/1573398X16999200819151645
Rapisarda V, Caltabiano R, Musumeci G, Castrogiovanni P, Ferrante M, Ledda C, et al. Analysis of fibulin-3 after exposure to asbestos-like fibers Environ Res 2017;156:381-87.
DOI: https://doi.org/10.1016/j.envres.2017.03.055
Brody AR. How inhaled asbestos causes scarring and cancer. Curr Respir Med Rev 2018;14:204-17.
DOI: https://doi.org/10.2174/1573398X15666181231145538
Broggi G, Filetti V, Magro G, Morante B, Garro R, Ledda C, et al. Immunohistochemical expression of cAMP in fluoroedenite induced malignant pleural mesothelioma: Preliminary results. Mol Med Rep 2023;28:132.
Rapisarda V, Broggi G, Caltabiano R, Lombardo C, Castorina S, Trovato A, et al. ATG7 immunohistochemical expression in malignant pleural mesothelioma. A preliminary report. Histol Histopathol 2021;36:1301-8.
Moody TW, Jensen RT. VIP and PACAP: recent insights into their functions/roles in physiology and disease from molecular and genetic studies. Curr Opin Endocrinol Diabetes Obes 2006;13:107-15.
Vaudry D, Falluel-Morel A, Bourgault S. Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 2009;61:283-357.
DOI: https://doi.org/10.1124/pr.109.001370
Arimura A, Shioda S. Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interaction. Front Neuroendocrinol 1995;16:53-88.
DOI: https://doi.org/10.1006/frne.1995.1003
Arimura A. Perspectives on pituitary adenylate cyclase-activating polypeptide (PACAP) in the neuroendocrine, endocrine, and nervous systems. J Recept Signal Transduct Res 1998;18:533-65.
DOI: https://doi.org/10.2170/jjphysiol.48.301
Waschek JA. VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair. Brit J Pharmacol 2002;137:1005-18.
D'Amico AG, Maugeri G, Magrì B, Lombardo C, Saccone S, Federico C, et al. PACAP-ADNP axis prevents outer retinal barrier breakdown and choroidal neovascularization by interfering with VEGF secreted from retinal pigmented epitelium cells. Peptides 2023;168:171065.
DOI: https://doi.org/10.1016/j.peptides.2023.171065
D'Amico AG, Maugeri G, Vanella L, Pittalà V, Reglodi D, D'Agata V. Multimodal role of PACAP in glioblastoma. Brain Sci. 2021;11:994.
DOI: https://doi.org/10.3390/brainsci11080994
Maugeri G, D'Amico AG, Saccone S, Federico C, Rasà DM, Caltabiano R, et al. Effect of PACAP on hypoxia-induced angiogenesis and epithelial-mesenchymal transition in glioblastoma. Biomedicines. 2021;9:965.
DOI: https://doi.org/10.3390/biomedicines9080965
Maugeri G, D'Amico AG, Reitano R, Magro G, Cavallaro S, Salomone S, D'Agata V. PACAP and VIP inhibit the invasiveness of glioblastoma cells exposed to hypoxia through the regulation of HIFs and EGFR expression. Front Pharmacol 2016;7:139.
DOI: https://doi.org/10.3389/fphar.2016.00139
Maugeri G, D'Amico AG, Rasà DM, Saccone S, Federico C, Cavallaro S, D'Agata V. PACAP and VIP regulate hypoxia-inducible factors in neuroblastoma cells exposed to hypoxia. Neuropeptides 2018;69:84-91.
DOI: https://doi.org/10.1016/j.npep.2018.04.009
Noh KT, Kim HJ, Kim MS. PACAP inhibits tumor growth and interferes with clusterin in cervical carcinomas. Oncol Reports 2015;34:163-70.
Juhász T, Matta C, Katona É, Somogyi C, Takács R, Hajdú T, et al. Pituitary adenylate cyclase-activating polypeptide (PACAP) signalling enhances osteogenesis in UMR-106 cell line. J Mol Neurosci 2014;54:555-73.
DOI: https://doi.org/10.1007/s12031-014-0389-1
Le SV, Yamaguchi DJ, McArdle CA, Tachiki K, Pisegna JR, Germano P. PAC1 and PACAP expression, signaling, and effect on the growth of HCT8, human colonic tumour cells. Regul Pept 2002;109:115-25.
DOI: https://doi.org/10.1016/S0167-0115(02)00194-5
Dacic S. Pleural mesothelioma classification-update and challenges. Mod Pathol 2022;35:51-6.
DOI: https://doi.org/10.1038/s41379-021-00895-7
Broggi G, Angelico G, Filetti V, Ledda C, Lombardo C, Vitale E, et al. Immunohistochemical expression of serine and arginine-rich splicing factor 1 (SRSF1) in fluoro-edenite-induced malignant mesothelioma: a preliminary study. Int J Environ Res Public Health 2021;18:6249.
DOI: https://doi.org/10.3390/ijerph18126249
Loreto C, Lombardo C, Caltabiano R, Ledda C, Hagnas M, Filetti V, et al. In vivo immunohistochemical study on macroH2A.1 in lung and lymph-node tissues exposed to an asbestiform fiber. Curr Mol Med 2020;20:653-660.
DOI: https://doi.org/10.2174/1566524020666200220130023
Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun.1989;164:567-74.
DOI: https://doi.org/10.1016/0006-291X(89)91757-9
Sandor B, Fintor K, Reglodi D, Fulop DB, Helyes Z, Szanto I, et al. Structural and morphometric comparison of lower incisors in PACAP-deficient and wild-type mice. J Mol Neurosci 2016;59:300-8.
DOI: https://doi.org/10.1007/s12031-016-0765-0
Solés-Tarrés I, Cabezas-Llobet N, Vaudry D, Xifró X. Protective effects of pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide against cognitive decline in neurodegenerative diseases. Front Cell Neurosci 2020;14:221.
DOI: https://doi.org/10.3389/fncel.2020.00221
Reglodi D, Kiss P, Lubics A, Tamas A. Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr Pharm Des 2011;17:962-72.
DOI: https://doi.org/10.2174/138161211795589355
Waschek JA. VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair. Br J Pharmacol 2013;169:512-23.
DOI: https://doi.org/10.1111/bph.12181
D'Amico AG, Maugeri G, Saccone S, Federico C, Cavallaro S, Reglodi D, D'Agata V. PACAP modulates the autophagy process in an in vitro model of amyotrophic lateral sclerosis. Int J Mol Sci 2020;21:2943.
DOI: https://doi.org/10.3390/ijms21082943
Maugeri G, D'Amico AG, Morello G, Reglodi D, Cavallaro S, D'Agata V. Differential vulnerability of oculomotor versus hypoglossal nucleus during ALS: involvement of PACAP. Front Neurosci 2020;14:805.
DOI: https://doi.org/10.3389/fnins.2020.00805
Maugeri G, D'Amico AG, Musumeci G, Reglodi D, D'Agata V. Effects of PACAP on Schwann cells: focus on nerve injury. Int J Mol Sci 2020;21:8233.
DOI: https://doi.org/10.3390/ijms21218233
Reubi JC, Läderach U, Waser B, Gebbers JO, Robberecht P, Laissue JA. Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res 2000;60:3105-12.
Schulz S, Röcken C, Mawrin C, Weise W, Höllt V, Schulz S. Immunocytochemical identification of VPAC1, VPAC2, and PAC1 receptors in normal and neoplastic human tissues with subtype-specific antibodies. Clin Cancer Res 2004;10:8235-42.
DOI: https://doi.org/10.1158/1078-0432.CCR-04-0939
Cochaud S, Meunier AC, Monvoisin A, Bensalma S, Muller JM, Chadéneau C. Neuropeptides of the VIP family inhibit glioblastoma cell invasion. J Neurooncol 2015;122:63-73.
DOI: https://doi.org/10.1007/s11060-014-1697-6
Zibara K, Zeidan A, Mallah K, Kassem N, Awad A, Mazurier F, et al. Signaling pathways activated by PACAP in MCF-7 breast cancer cells. Cell Signal 2018;50:37-47.
DOI: https://doi.org/10.1016/j.cellsig.2018.06.009
Dickson L, Finlayson K. VPAC and PAC receptors: From ligands to function. Pharmacol Ther 2009;121:294-316.
DOI: https://doi.org/10.1016/j.pharmthera.2008.11.006
Dazzi H, Hasleton PS, Thatcher N, Wilkes S, Swindell R, Chatterjee AK. Malignant pleural mesothelioma and epidermal growth factor receptor (EGF-R). Relationship of EGF-R with histology and survival using fixed paraffin embedded tissue and the F4, monoclonal antibody. Br J Cancer 1990;61:924-6.
DOI: https://doi.org/10.1038/bjc.1990.207
Destro A, Ceresoli GL, Falleni M, Zucali PA, Morenghi E, Bianchi P, et al. EGFR overexpression in malignant pleural mesothelioma. An immunohistochemical and molecular study with clinico-pathological correlations. Lung Cancer 2006;51:207-15.
DOI: https://doi.org/10.1016/j.lungcan.2005.10.016
Chia PL, Parakh S, Russell P, Gan HK, Asadi K, Gebski V, et al. Expression of EGFR and conformational forms of EGFR in malignant pleural mesothelioma and its impact on survival. Lung Cancer 2021;153:35-41.
DOI: https://doi.org/10.1016/j.lungcan.2020.12.028
Maugeri G, D'Amico AG, Castrogiovanni P, Saccone S, Federico C, Reibaldi M, et al. PACAP through EGFR transactivation preserves human corneal endothelial integrity. J Cell Biochem 2019;120:10097-105.
DOI: https://doi.org/10.1002/jcb.28293
Moody TW, Lee L, Iordanskaia T, Ramos-Alvarez I, Moreno P, Boudreau HE, et al. PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner. Peptides 2019;120:170017.
DOI: https://doi.org/10.1016/j.peptides.2018.09.005
Supporting Agencies
Piano di Incentivi per la ricerca di Ateneo 2020/2022 Linea di intervento 2How to Cite
Lombardo, C., Maugeri, G., D’Amico, A. G., Broggi, G., Caltabiano, R., Filetti, V., … Loreto, C. (2024). Pleural mesothelioma from fluoro-edenite exposure: PACAP and PAC1 receptor. A preliminary report. European Journal of Histochemistry, 68(2). https://doi.org/10.4081/ejh.2024.3994
Copyright (c) 2024 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- M Cotrufo, L De Santo, A Della Corte, F Di Meglio, G Guerra, C Quarto, S Vitale, C Castaldo, S Montagnani, Basal lamina structural alterations in human asymmetric aneurismatic aorta , European Journal of Histochemistry: Vol. 49 No. 4 (2005)
- G Abban, NB Yildirim, AM Jetten, Regulation of the vitamin D receptor and cornifin beta expression in vaginal epithelium of the rats through vitamin D3 , European Journal of Histochemistry: Vol. 52 No. 2 (2008)
- I. Janiuk, I. Kasacka, Quantitative evaluation of CART-containing cells in urinary bladder of rats with renovascular hypertension , European Journal of Histochemistry: Vol. 59 No. 2 (2015)
You may also start an advanced similarity search for this article.
