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Neural changes within the pancreatic tumor microenvironment involve microglia and Schwann cells, which can regulate immune responses, facilitate nerve invasion, and exacerbate cancer pain via neural growth factor and tropomyosin receptor kinase A signaling. Targeting neural invasion may improve prognosis and reduce pain.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/unraveling-the-connection-pancreatic-cancer-cells-and-schwann-cells-academic-article/327269/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/unraveling-the-connection-pancreatic-cancer-cells-and-schwann-cells-academic-article/327269.png","ImageObject",300,407,{"name":42,"@type":43},"Olivia Brown","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does neural invasion play in pancreatic ductal adenocarcinoma?","Question",{"text":63,"@type":64},"Neural invasion is a key pathological hallmark in pancreatic ductal adenocarcinoma and shows high prevalence compared with other solid tumors. It damages neural sheaths and is associated with increased neural density and remodeling, contributing to neuropathic and inflammatory pain.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How are different types of neural invasion classified?",{"text":68,"@type":64},"Neural invasion can be epineural, perineural, or endoneural. Epineural invasion involves direct cancer cell contact without penetration of the epineurium, perineural invasion places cells within the perineural sheet, and endoneural invasion reflects penetration through the perineurium into the endoneural sheet.",{"name":70,"@type":61,"acceptedAnswer":71},"Why might Schwann cells influence tumor progression and cancer pain?",{"text":72,"@type":64},"Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting multiple factors. They can support tumor invasion of nerves and distant metastasis and contribute to pain by releasing pain-related molecules such as neural growth factor that activates sensory neuron pathways through tropomyosin receptor kinase A.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},327269,1790495549,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":111,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":117},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Communication  \nUnraveling the Connection: Pancreatic Cancer Cells and Schwann Cells  \nIngrid Garajová 1, *, Francesca Trentini 1, Francesco Leonardi 1 and Elisa Giovannetti 2,3,4  \nCitation: Garajová, I.; Trentini, F.; Leonardi, F.; Giovannetti, E.  \nUnraveling the Connection: Pancreatic Cancer Cells and Schwann Cells. J. Clin. Med. 2024, 13, 1785 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)jcm13061785  \nAcademic Editor: Kelvin K. NG  \nReceived: 27 February 2024  \nRevised: 16 March 2024  \nAccepted: 18 March 2024  \nPublished: 20 March 2024  \nCopyright: © 2024 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 Medical Oncology Unit, University Hospital of Parma, 43100 Parma, Italy; [francesca.trentini@unipr.it](francesca.trentini@unipr.it) (F.T.); [il-france@hotmail.com](il-france@hotmail.com) (F.L.)  \n2 Department of Medical Oncology, Lab of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, VU University Medical Center (VUmc), 1007 MB Amsterdam, The Netherlands; [elisa.giovannetti@gmail.com](elisa.giovannetti@gmail.com)  \n[3](3 Cancer Pharmacology Lab)[ Cancer Pharmacology Lab](3 Cancer Pharmacology Lab), [AIRC Start-Up Unit](AIRC Start-Up Unit), [56017 Pisa](56017 Pisa), [Italy](Italy)  \n4 Fondazione Pisana per la Scienza, 56017 San Giuliano Terme, Italy  \n* Correspondence: [ingegarajova@gmail.com](ingegarajova@gmail.com); Tel.: +39-52-1702-660  \nAbstract: Pancreatic ductal adenocarcinoma is one of the most lethal solid malignancies, characterized by its aggressiveness and metastatic potential, with a 5-year survival rate of only 13% . Progress in the management of metastatic disease has been modest. A robust connection between nervous system and tumor progression exists, with prominent neural alterations having been observed during pancreatic cancer’s progression, including neural hypertrophy, neural density, and neural remodeling. The pancreatic tumor microenvironment includes s set of cells and structures that constantly dialogue with cancer cells, influencing its growth and behavior. The microglia is key cellular components of the tumor microenvironment, and Schwann cells are the principal glial cells in the peripheral neural system. Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting a variety of factors and can support a tumor’s invasion of nerves and distant metastasis, with further pain exacerbation. Schwann cells secrete various pain-related molecules, such as the neural growth factor, to mediate the activation of primary sensory neurons, leading to pain induction. The binding of the neural growth factor to tropomyosin receptor kinase A isan important signaling mechanism for pain perception in humans. Consequently, directing efforts towards targeting neural invasion may provide an alternative strategy to improve the prognosis of and alleviate pain in patients with pancreatic cancer.  \nKeywords: pancreatic ductal adenocarcinoma; neural invasion; Schwann cells; tumor microenvironment; cancer pain  \n1. Neural Invasion in Pancreatic Cancer  \nPancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all major solid tumors and is currently the fourth leading cause of cancer-related deaths, with a 5-year overall survival (OS) rate of only 13%[1] . One of the pathological hallmarks of PDAC is neural invasion (NI). Among all solid tumors, NI has the highest prevalence in PDAC [2–4] . Interestingly, only about 25% of the early stages of PDAC do not present NI, suggesting that it could represent an early symptomatic phase of cancer progression. Cancer invasion damages the neural sheath and correlates with increased neural density an","cbCaieJgiWTEHmmt","https://ap.wps.com/l/cbCaieJgiWTEHmmt","pdf",654431,"English","# Abstract\n# Neural Invasion in Pancreatic Cancer\n## Definition and prevalence\n## Types of neural invasion\n## Clinical relevance and pain correlation","[{\"question\":\"What role does neural invasion play in pancreatic ductal adenocarcinoma?\",\"answer\":\"Neural invasion is a key pathological hallmark in pancreatic ductal adenocarcinoma and shows high prevalence compared with other solid tumors. It damages neural sheaths and is associated with increased neural density and remodeling, contributing to neuropathic and inflammatory pain.\"},{\"question\":\"How are different types of neural invasion classified?\",\"answer\":\"Neural invasion can be epineural, perineural, or endoneural. Epineural invasion involves direct cancer cell contact without penetration of the epineurium, perineural invasion places cells within the perineural sheet, and endoneural invasion reflects penetration through the perineurium into the endoneural sheet.\"},{\"question\":\"Why might Schwann cells influence tumor progression and cancer pain?\",\"answer\":\"Schwann cells can regulate changes in the tumor microenvironment and immune responses by secreting multiple factors. They can support tumor invasion of nerves and distant metastasis and contribute to pain by releasing pain-related molecules such as neural growth factor that activates sensory neuron pathways through tropomyosin receptor kinase A.\"}]","Unraveling the Connection: Pancreatic Cancer Cells and Schwann Cells - Academic Article | PDF",1789976858]