[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-406385-105":59,"doc-detail-406385-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","elevated-serum-gastrin-is-associated-with-melanoma-progression-putative-role-in-increased-migration-and-invasion-of-melanoma-cells","Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells","","Micro-environmental signals, including stromal and immune cells, cytokines, and circulating hormones, influence cancer progression. The study tested how gastrin affects melanoma cells in 89 patients, linking circulating gastrin with melanoma thickness and metastasis. CCK2R expression was verified by immunocytochemistry, and TCGA analysis showed higher CCKBR mRNA in stage III–IV tumors. In melanoma cell lines, gastrin increased intracellular calcium, promoted migration and invasion, altered MMP-2 and TIMP-3, and dermal fibroblasts enhanced invasion. The results support elevated serum gastrin as a risk factor and suggest CCK2R-mediated mechanisms in both tumor and adjacent stromal cells.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/elevated-serum-gastrin-is-associated-with-melanoma-progression-putative-role-in-increased-migration-and-invasion-of-melanoma-cells/406385/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/elevated-serum-gastrin-is-associated-with-melanoma-progression-putative-role-in-increased-migration-and-invasion-of-melanoma-cells/406385.png","ImageObject",300,407,{"name":92,"@type":93},"Bulrr","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-07","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How is gastrin linked to melanoma progression in patients?","Question",{"text":112,"@type":113},"In 89 melanoma patients, circulating gastrin concentrations showed a statistically significant association with melanoma thickness and metastasis, which are established risk factors for progression and prognosis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What evidence supports CCK2R/CCKBR involvement?",{"text":117,"@type":113},"A validated antibody confirmed weak to moderate CCK2R expression in primary malignant melanoma cells and melanoma cell lines. In the Skin Cutaneous Melanoma TCGA dataset, higher CCKBR mRNA levels correlated with stage III–IV compared with stage I–II melanomas.",{"name":119,"@type":110,"acceptedAnswer":120},"What cellular effects does gastrin have on melanoma cells?",{"text":121,"@type":113},"In melanoma cell lines, gastrin increased intracellular calcium and stimulated migration and invasion. Proteomic findings indicated increased MMP-2 and reduced TIMP-3 in response to gastrin, and fibroblasts/myofibroblasts further increased gastrin-induced invasion.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},406385,1790842457,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":36,"preview_page_count":4},5909892115043,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Article  \nElevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells  \nAkos Janos Varga 1,2, Istvan Balazs Nemeth 2, Lajos Kemeny 2, Janos Varga 2, Laszlo Tiszlavicz 3, Dinesh Kumar 1, Steven Dodd 1, Alec W. M. Simpson 1, Tunde Buknicz 2, Rob Beynon 4, Deborah Simpson 4, Tibor Krenacs 5, *, Graham J. Dockray 1 and Andrea Varro 1  \nCitation: Varga, A.J.; Nemeth, I.B.; Kemeny, L.; Varga, J.; Tiszlavicz, L.; Kumar, D.; Dodd, S.; Simpson,  \nA.W.M.; Buknicz, T.; Beynon, R.; et al. Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells. Int. J. Mol. Sci. 2023, 24, 16851. [https://](https://)[ ](https://)[doi.org/10.3390/ijms242316851](doi.org/10.3390/ijms242316851)  \nAcademic Editor: Guendalina Lucarini  \nReceived: 9 October 2023  \nRevised: 3 November 2023  \nAccepted: 17 November 2023  \nPublished: 28 November 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 7BE, UK; [g.j.dockray@liverpool.ac.uk](g.j.dockray@liverpool.ac.uk) (G.J.D.); [avarro@liverpool.ac.uk](avarro@liverpool.ac.uk) (A.V.)  \n2 Department of Dermatology and Allergology, University of Szeged, 6720 Szeged, Hungary  \n3 Department of Pathology, University of Szeged, 6725 Szeged, Hungary  \n4 Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7BE, UK  \n5 Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary  \n* Correspondence: [krenacs.tibor@semmelweis.hu](krenacs.tibor@semmelweis.hu)  \nAbstract: Micro-environmental factors, including stromal and immune cells, cytokines, and circulating hormones are well recognized to determine cancer progression. Melanoma cell growth was recently shown to be suppressed by cholecystokinin/gastrin (CCK) receptor antagonists, and our preliminary data suggested that melanoma patients with Helicobacter gastritis (which is associated with elevated serum gastrin) might have an increased risk of cancer progression. Therefore, in the present study, we examined how gastrin may act on melanoma cells. In 89 melanoma patients, we found a statistically significant association between circulating gastrin concentrations and melanoma thickness and metastasis, which are known risk factors of melanoma progression and prognosis. Immunocytochemistry using a validated antibody confirmed weak to moderate CCK2R expression in both primary malignant melanoma cells and the melanoma cell lines SK-MEL-2 and G361 . Furthermore, among the 219 tumors in the Skin Cutaneous Melanoma TCGA Pan-Cancer dataset showing gastrin receptor (CCKBR) expression, significantly higher CCKBR mRNA levels were linked to stage III–IV than stage I–II melanomas. In both cell lines, gastrin increased intracellular calcium levels and stimulated cell migration and invasion through mechanisms inhibited by a CCK2 receptor antagonist. Proteomic studies identified increased MMP-2 and reduced TIMP-3 levels in response to gastrin that were likely to contribute to the increased migration of both cell lines. However, the effects of gastrinon tumor cell invasion were relatively weak in the presence of the extracellular matrix. Nevertheless, dermal fibroblasts/myofibroblasts, known also to express CCK2R, increased gastrin-induced cancer cell invasion. Our data suggest that in a subset of melanoma patients, an elevated serum gastrin concentration is a risk factor for melanoma tumor progression, and that gastrin may act on both mel","cbCaie2UMsSzYRKD","https://ap.wps.com/l/cbCaie2UMsSzYRKD","pdf",4431258,16,"English","# Abstract\n# Introduction\n## Micro-environmental factors in cancer progression\n## Gastrin biology and CCK2R signaling\n## Gastrin expression in tumors and implications for melanoma","[{\"question\":\"How is gastrin linked to melanoma progression in patients?\",\"answer\":\"In 89 melanoma patients, circulating gastrin concentrations showed a statistically significant association with melanoma thickness and metastasis, which are established risk factors for progression and prognosis.\"},{\"question\":\"What evidence supports CCK2R/CCKBR involvement?\",\"answer\":\"A validated antibody confirmed weak to moderate CCK2R expression in primary malignant melanoma cells and melanoma cell lines. In the Skin Cutaneous Melanoma TCGA dataset, higher CCKBR mRNA levels correlated with stage III–IV compared with stage I–II melanomas.\"},{\"question\":\"What cellular effects does gastrin have on melanoma cells?\",\"answer\":\"In melanoma cell lines, gastrin increased intracellular calcium and stimulated migration and invasion. Proteomic findings indicated increased MMP-2 and reduced TIMP-3 in response to gastrin, and fibroblasts/myofibroblasts further increased gastrin-induced invasion.\"}]","Elevated Serum Gastrin Is Associated with Melanoma Progression: Putative Role in Increased Migration and Invasion of Melanoma Cells | PDF",1790565261]