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The article explains metastasis as the spread of neoplastic cells from the primary tumor via blood and lymph and reviews the “Seed and Soil” framework and newer contributors. It focuses on extracellular vesicles (EVs) and their cargo transfer—through uptake by recipient cells at distinct anatomical sites—as a key event in cell transformation and metastasis induction, including EV pathways delivering cargo into recipient nuclei.",{"@graph":69,"@context":123},[70,84,106],{"@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/horizontal-transfer-of-malignant-traits-and-the-involvement-of-extracellular-vesicles-in-metastasis-abstract-introduction-and-ev-pathways/380111/",{"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/horizontal-transfer-of-malignant-traits-and-the-involvement-of-extracellular-vesicles-in-metastasis-abstract-introduction-and-ev-pathways/380111.png","ImageObject",300,407,{"name":92,"@type":93},"Margaret","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is metastasis, according to the article?","Question",{"text":113,"@type":114},"Metastasis is the spread of cancer cells from the primary site to distant tissues and/or organs, occurring through blood and lymphatic dissemination.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does the article describe the classical “Seed and Soil” hypothesis?",{"text":118,"@type":114},"It states that metastases are organ-specific: the “soil” (the tissue environment) supports growth of the “seed” (tumor cells with metastatic potential) through interactions with host organ components.",{"name":120,"@type":111,"acceptedAnswer":121},"What role do extracellular vesicles (EVs) play in metastasis?",{"text":122,"@type":114},"EVs are described as mediators of intercellular communication that can favor metastasis, including transferring EV-associated biomolecules that may contribute to cell transformation and metastatic induction.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},380111,1790630752,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},137451207643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","cells  \nReview  \nHorizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis  \nGoffredo O. Arena 1,2,3, Stefano Forte 3, Mohamed Abdouh 4, Cheryl Vanier 5, Denis Corbeil 6 and Aurelio Lorico 3,5, *  \nCitation: Arena, G.O.; Forte, S.; Abdouh, M.; Vanier, C.; Corbeil, D.; Lorico, A. Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis. Cells 2023, 12, 1566 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells12121566  \nAcademic Editor: Maurizio Onisto  \nReceived: 21 April 2023  \nRevised: 31 May 2023  \nAccepted: 2 June 2023  \nPublished: 6 June 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 Surgery, McGill University, Montr²al, QC H3A 0G4, Canada; [goffredo.arena@gmail.com](goffredo.arena@gmail.com)  \n[2](2 Fondazione Istituto G. Giglio)[ Fondazione Istituto G. Giglio](2 Fondazione Istituto G. Giglio), [90015 Cefal](90015 Cefal)ò, Italy  \n3 Mediterranean Institute of Oncology, 95029 Viagrande, Italy; [stefano.forte@grupposamed.com](stefano.forte@grupposamed.com)  \n4 Cancer Research Program, Research Institute, McGill University Health Centre, Montr²al, QC H3A 0G4, Canada; [mohamed.abdouh@mcgill.org](mohamed.abdouh@mcgill.org)  \n5 Touro University Nevada College of Medicine, Henderson, NV 89014, USA; [cvanier@touro.edu](cvanier@touro.edu)  \n6 Biotechnology Center (BIOTEC) and Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, 01307 Dresden, Germany; denis.corbeil@tu-dresden.de  \n* Correspondence: [alorico@touro.edu](alorico@touro.edu)  \nAbstract: Metastases are responsible for the vast majority of cancer deaths, yet most therapeutic efforts have focused on targeting and interrupting tumor growth rather than impairing the metastatic process. Traditionally, cancer metastasis is attributed to the dissemination of neoplastic cells from the primary tumor to distant organs through blood and lymphatic circulation. A thorough understanding of the metastatic process is essential to develop new therapeutic strategies that improve cancer survival. Since Paget's original description of the “Seed and Soil” hypothesis over a hundred years ago, alternative theories and new players have been proposed. In particular, the role of extracellular vesicles (EVs) released by cancer cells and their uptake by neighboring cells or at distinct anatomical sites has been explored. Here, we will outline and discuss these alternative theories and emphasize the horizontal transfer of EV-associated biomolecules as a possibly major event leading to cell transformation and the induction of metastases. We will also highlight the recently discovered intracellular pathway used by EVs to deliver their cargoes into the nucleus of recipient cells, which is a potential target for novel anti-metastatic strategies.  \nKeywords: cancer; metastasis; nucleoplasmic reticulum; extracellular vesicles; exosomes; oncogene; tumor suppressor gene; microenvironment  \n1. Introduction  \nMetastasis is defined as the spread of cancer cells from the primary site of formation to distant tissues and/or organs. Such spatiotemporal cellular dissemination that occurs through the blood and lymphatic system is considered tobe responsible for the vast majority of cancer deaths worldwide [1] . A deeper understanding of metastasis might identify new mechanisms that could be intercepted, leading to new anti-cancer therapeutic strategies. The classic hypothesis of the metastatic process is based on Stephen Paget's “Seed and Soil” model, according to which the distribution of metastases is not casual, but organspecific: the “s","cbCaighDxuuZLupt","https://ap.wps.com/l/cbCaighDxuuZLupt","pdf",4179420,27,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What is metastasis, according to the article?\",\"answer\":\"Metastasis is the spread of cancer cells from the primary site to distant tissues and/or organs, occurring through blood and lymphatic dissemination.\"},{\"question\":\"How does the article describe the classical “Seed and Soil” hypothesis?\",\"answer\":\"It states that metastases are organ-specific: the “soil” (the tissue environment) supports growth of the “seed” (tumor cells with metastatic potential) through interactions with host organ components.\"},{\"question\":\"What role do extracellular vesicles (EVs) play in metastasis?\",\"answer\":\"EVs are described as mediators of intercellular communication that can favor metastasis, including transferring EV-associated biomolecules that may contribute to cell transformation and metastatic induction.\"}]","Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis - Abstract, Introduction, and EV Pathways | PDF",1790238781,68]