[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-326959-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-326959-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","malignant-tumor-cells-engender-second-membrane-lined-organelles-for-self-protection-and-tumor-progression","Malignant tumor cells engender second membrane-lined organelles for self-protection and tumor progression","","Malignant transformation drives aggressive oncocells to generate a second membrane outside the plasma membrane, forming cytocapsulas (CCs) and cytocapsular tubes (CCTs). Together these structures constitute cytocapsular oncocells with pleiotropic functions in vivo, appearing broadly in solid cancers and in immune organs for hematologic cancers. Proteomic and biochemical work identifies the PMCA2 calcium pump as highly up-regulated in CCs and CCTs in malignant tumors, supporting a distinct biomarker and therapy target. Cytocapsular tumor networks also enable metastasis routes by protected cell dissemination.",{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/malignant-tumor-cells-engender-second-membrane-lined-organelles-for-self-protection-and-tumor-progression/326959/",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/malignant-tumor-cells-engender-second-membrane-lined-organelles-for-self-protection-and-tumor-progression/326959.png","ImageObject",300,407,{"name":42,"@type":43},"Patrick","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What second membrane-lined organelles do malignant tumor cells form?","Question",{"text":63,"@type":64},"They form cytocapsulas (CCs) and cytocapsular tubes (CCTs), creating cytocapsular oncocells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which biomarker is up-regulated in CCs and CCTs in malignant tumors?",{"text":68,"@type":64},"The PMCA2 calcium pump is highly up-regulated in CCs and CCTs in malignant tumors.",{"name":70,"@type":61,"acceptedAnswer":71},"How do cytocapsular tumor networks relate to metastasis and dissemination?",{"text":72,"@type":64},"They produce many CCTs that act as pathways for metastasis and can invade micro blood vessels to release cytocapsular oncocells into circulation.","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},326959,1791111102,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,105,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"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":111,"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":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":112,"preview_page_count":4},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","RESEARCH ARTICLE  \nCELL BIOLOGY  \n OPEN ACCESS  \nMalignant tumor cells engender second membrane-lined organelles for self-protection and tumor progression  \nTingfang Yia, b,1 and Gerhard Wagnera, b,c,1  \nContributed by Gerhard Wagner; received October 4, 2023; accepted December 14, 2023; reviewed by Wolfgang Baumeister, Davide Ruggero, and Peter Sarnow  \nCancer is a leading cause of mortality in humans, but the efficacy of current treatments for many cancers is limited, as they lack unique mechanistically defined targets. Here, we show that, upon malignant transformation, aggressive oncocells generate a second membrane exterior to their plasma membrane to form cytocapsulas (CCs) and cytocapsular tubes (CCTs), which all together constitute cytocapsular oncocells with pleotropic biological functions in cancer patient tissues in vivo. Proteomic and biochemical analyses revealed that the PMCA2 calcium pump is highly up-regulated in CCs and CCTs in malignant tumors but not in normal tissues, thus identifying a unique cancer biomarker and target for cancer therapy. Cytocapsular oncocells are universally present in solid cancers and appear in hematologic cancers in immune organs. Multi-cell malignant tumors are also enveloped by protective CC membranes. These cytocapsular tumors (CTs) generate numerous CCTs that form freeways for cancer cell metastasis to both neighboring and distant destinations. Entire cytocapsular tumor networks (CTNs) dominate physical cancer metastasis pathways in cancer patients in vivo. Later, CCTs invade micro blood vessels and release cytocapsular oncocells into the blood, providing a source of circulating tumor cells. CTNs interconnect cytocapsular tumors in primary and secondary cancer niches, creating larger cytocapsular tumor network systems (CTNSs) . Primary and secondary CTNSs are in turn interconnected, forming dynamic and integrated CTNSs. Thus, interconnected cytocapsular oncocells, CTNs, and CTNSs coordinate cancer progression via the integrated cytocapsular membrane systems.  \ncancer | cytocapsular oncocell | cytocapsular tube | cytocapsular tumor | PMCA2  \nCuring cancer is among the most urgent challenges facing human health care (1–3) . Almost 10 million cancer deaths and around 19.3 million new cancer cases occurred worldwide in 2020 alone (4) . Over the last decades, many aspects of cancer progression have been studied intensively (5–11) . Several models have been hypothesized for tumor progression, which together propose a diverse array of possible driving factors, including genetic alterations, genomic aberrations (discordant inheritance, DNA macro-alterations), oncoprotein promotion, signaling pathways, cell plasticity, intercellular reactions, and microenvironments (12–21). However, current clinical cancer treatment outcomes suggest that the mechanisms underlying cancer development and progression in vivo have not been fully resolved (22–24) .  \nRecently, we reported that aggressive cancer cells engender a second membrane outside the plasma membrane in vitro, named cytocapsula (CC) or cytocapsular tube (CCT) (25) . Here, we present an in-depth investigation of the biology of these previously unrecognized organelles and their links to cancer progression in vivo. We identified a biomarker Ca2+ -ATPase 2 (PMCA2, or ATP2B2) (26–29) for the CC/CCT membrane, which allowed us to reveal the lifecycle of cytocapsular oncocells both in vitro and in vivo. Wereport a series of previously undocumented cancer phenomena, such as prophase-cytocapsular tumors (PCTs), cytocapsular tumor (CT), nuperphase tumor (NT), acytocapsular oncocell mass-CC/CCT complex (AMCC), cytocapsulasome, cytocapsular tumor network system (CTNS), and integrated primary and secondary CTNSs. This report expands our understanding of cancer progression in vivo to include cytocapsular membrane network-shielded oncocell devolution and evolution systems.  \nResults  \nIdentification of PMCA2 As a Biomarker for Cytocapsulas and Cytocapsular","cbCaijd0YiaBJigT","https://ap.wps.com/l/cbCaijd0YiaBJigT","pdf",12233623,12,"English","# Malignant tumor cells generate second membrane-lined organelles\n## Cytocapsulas and cytocapsular tubes form cytocapsular oncocells\n## PMCA2 as a cancer biomarker and therapy target\n## Cytocapsular tumor networks and metastasis pathways\n## Integrated cytocapsular membrane systems in tumor progression","[{\"question\":\"What second membrane-lined organelles do malignant tumor cells form?\",\"answer\":\"They form cytocapsulas (CCs) and cytocapsular tubes (CCTs), creating cytocapsular oncocells.\"},{\"question\":\"Which biomarker is up-regulated in CCs and CCTs in malignant tumors?\",\"answer\":\"The PMCA2 calcium pump is highly up-regulated in CCs and CCTs in malignant tumors.\"},{\"question\":\"How do cytocapsular tumor networks relate to metastasis and dissemination?\",\"answer\":\"They produce many CCTs that act as pathways for metastasis and can invade micro blood vessels to release cytocapsular oncocells into circulation.\"}]","Malignant tumor cells engender second membrane-lined organelles for self-protection and tumor progression | PDF",1789975858]