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The theory extends Otto Aichel’s century-old cell-fusion concept by specifying the macrophage subtype as memory/trained rather than naïve or effector. By linking macrophage immune memory behaviors—dormancy/quiescence, awakening by primers, and stem-like self-renewal—to metastatic cancer-cell traits, it aims to explain clinical paradoxes, dormancy, and recurrence-versus-regression patterns, and outlines potential therapeutic strategies.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/hypothesis-hematogenous-metastatic-cancer-cells-of-solid-tumors-may-disguise-themselves-as-memory-macrophages-for-metastasis-theory-and-hypothesis/332244/",{"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/hypothesis-hematogenous-metastatic-cancer-cells-of-solid-tumors-may-disguise-themselves-as-memory-macrophages-for-metastasis-theory-and-hypothesis/332244.png","ImageObject",300,407,{"name":92,"@type":93},"Noah","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-04","2026-09-21",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},"What central mechanism does the hypothesis propose for metastasis?","Question",{"text":112,"@type":113},"Metastatic cancer cells arise after fusion with a memory/trained macrophage, which enables the cancer cells to disguise themselves as memory macrophages and metastasize to distant organs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the hypothesis extend Otto Aichel’s original theory?",{"text":117,"@type":113},"It refines the fusion partner by arguing that the macrophage involved is specifically a memory/trained macrophage, not other macrophage subtypes, to account for dormancy and stem cell-like self-renewal.",{"name":119,"@type":110,"acceptedAnswer":120},"Which clinical or biological phenomena does the hypothesis aim to explain?",{"text":121,"@type":113},"It is proposed to explain puzzling cancer features such as recurrence versus regression effects, tumor regression from microbes or Coley’s toxin, drug-related anticancer activities, surgery/trauma-promoted metastasis, and microbiota impacts on tumors, and it suggests therapeutic strategies like Coley’s toxin-like preparations.","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},332244,1790193598,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"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},8796095462418,"https://ap-avatar.wpscdn.com/avatar/80000253c1241d02b47?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778826106357471780","TYPE Hypothesis and Theory PUBLISHED 05 July 2024  \nDOI 10.3389/fonc.2024.1412296  \nOPEN ACCESS  \nEDITED BY  \nAlberto N. Peo´n,  \nSociedad Española de Beneficencia, Mexico  \nREVIEWED BY  \nXiaoping Chen,  \nGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences (CAS), China  \nFlor Navarro,  \nUniversity of Zaragoza, Spain Gina Garcia-Romo,  \nLUMC, Netherlands Chiara Medaglia,  \nHˆopitaux Universitaires de Genève (HUG), Switzerland  \nCarlos Del Fresno,  \nHospital La Paz Institute for Health Research,(IdiPAZ), Spain  \n*CORRESPONDENCE Jiaxi Wu  \n[jxwu@sinh.ac.cn](jxwu@sinh.ac.cn)  \n†PRESENT ADDRESS Chuo Jiang,  \nShanghai Jiayin Biotechnology Co., Ltd. Shanghai, China  \n‡Retired  \nRECEIVED 04 April 2024  \nACCEPTED 19 June 2024  \nPUBLISHED 05 July 2024  \nCITATION  \nJiang C and Wu J (2024) Hypothesis: hematogenous metastatic cancer cells of solid tumors may disguise themselves as memory macrophages for metastasis.  \nFront. Oncol. 14:1412296 .  \ndoi: 10.3389/fonc.2024.1412296  \nCOPYRIGHT  \n© 2024 Jiang and Wu. This is an open-access article distributed under the terms of the  \nCreative Commons Attribution License (CC BY) .  \nThe use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nHypothesis: hematogenous metastatic cancer cells of solid tumors may disguise themselves as memory macrophages for metastasis  \nChuo Jiang 1,2† and Jiaxi Wu 2,3*‡  \n1School of Life Sciences, Shanghai University, Shanghai, China, 2Central Laboratories, Shanghai Clinical Research Center Xuhui Central Hospital, Chinese Academy of Sciences, Shanghai, China, 3Office of Industrial Cooperation, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China  \nGerman pathologist Otto Aichel suggested, a century ago, that the cancer cell acquired its metastatic property from a leukocyte via cell-cell fusion. Since then, several revised versions of this theory have been proposed. Most of the proposals attribute the generation of the metastatic cancer cell to the fusion between a primary cancer cell and a macrophage. However, these theories have not addressed several issues, such as dormancy and stem cell-like self-renewal, of the metastatic cancer cell. On the other hand, recent studies have found that, like T- and B-/plasma cells, macrophages can also be categorized into naïve, effector, and memory/trained macrophages. As a memory/trained macrophage can enter dormancy/quiescence, be awakened from the dormancy/quiescence by acquainted primers, and re-populate via stem cell-like self-renewal, we, therefore, further specify that the macrophage fusing with the cancer cell and contributing to metastasis, belongs with the memory/trained macrophage, not other subtypes of macrophages. The current theory can explain many puzzling clinical features of cancer, including the paradoxal effects (recurrence vs. regression) of microbes on tumors, “spontaneous” and Coley’s toxin-induced tumor regression, anticancer activities of b-blockers and anti-inflammatory/antiimmune/antibiotic drugs, oncotaxis, surgery-and trauma-promoted metastasis, and impact of microbiota on tumors. Potential therapeutic strategies, such as Coley’s toxin-like preparations, are proposed. This is the last article of our trilogy on carcinogenesis theories.  \nKEYWORDS  \nmetastasis, macrophage, trained macrophage, memory macrophage, fusion, hybridization, spontaneous regression, Coley’s toxin  \nFrontiers in Oncology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nAs a hallmark of cancer, metastasis is conceived as a unique intrinsic property of the primary cancer cell (priCaC) of solid tumors. On the other hand, German pathologist Otto Aichel proposed, more than a century ago, that the c","cbCaiedhcmtm1sGH","https://ap.wps.com/l/cbCaiedhcmtm1sGH","pdf",1251711,16,"English","# Introduction\n## Dormancy and self-renewal in metastatic cancer cells\n## Trained/memory macrophages and proposed scamouflage mechanism","[{\"question\":\"What central mechanism does the hypothesis propose for metastasis?\",\"answer\":\"Metastatic cancer cells arise after fusion with a memory/trained macrophage, which enables the cancer cells to disguise themselves as memory macrophages and metastasize to distant organs.\"},{\"question\":\"How does the hypothesis extend Otto Aichel’s original theory?\",\"answer\":\"It refines the fusion partner by arguing that the macrophage involved is specifically a memory/trained macrophage, not other macrophage subtypes, to account for dormancy and stem cell-like self-renewal.\"},{\"question\":\"Which clinical or biological phenomena does the hypothesis aim to explain?\",\"answer\":\"It is proposed to explain puzzling cancer features such as recurrence versus regression effects, tumor regression from microbes or Coley’s toxin, drug-related anticancer activities, surgery/trauma-promoted metastasis, and microbiota impacts on tumors, and it suggests therapeutic strategies like Coley’s toxin-like preparations.\"}]","Hypothesis: hematogenous metastatic cancer cells of solid tumors may disguise themselves as memory macrophages for metastasis - Theory and Hypothesis | PDF",1789997509]