[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382517-105":59,"doc-detail-382517-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","molecular-mechanisms-of-colorectal-liver-metastases","Molecular Mechanisms of Colorectal Liver Metastases","","The liver is the principal destination for metastasis in colorectal cancer, driven by portal circulation that links colon and rectum to the organ. The hepatic tumor microenvironment contains diverse cell types that regulate antigen recognition and immune activation. Distant primary tumors can “prime” the liver, forming a pre-metastatic niche. Metastasis proceeds through microvascular, extravascular pre-angiogenic, angiogenic, and growth phases, while exosomes shape distant niches. Targeting angiogenic and vascular mechanisms has been limited, so defining molecular drivers is essential to predict progression and treatment resistance.",{"@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/molecular-mechanisms-of-colorectal-liver-metastases/382517/",{"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/molecular-mechanisms-of-colorectal-liver-metastases/382517.png","ImageObject",300,407,{"name":92,"@type":93},"\tJames","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",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},"Why does colorectal cancer often metastasize to the liver?","Question",{"text":112,"@type":113},"Because portal vein circulation directly connects the colon and rectum to the liver, making the liver the most frequent target site for metastasis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What are the key phases in liver metastasis development?",{"text":117,"@type":113},"The process is described in four phases: a microvascular trapping phase, an extravascular pre-angiogenic phase, an angiogenic phase, and a growth phase where metastatic cells enlarge into detectable tumors.",{"name":119,"@type":110,"acceptedAnswer":120},"How do exosomes influence colorectal liver metastases?",{"text":121,"@type":113},"Exosomes transport proteins, lipids, and genetic information that can create a pre-metastatic niche in distant sites, including the liver.","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},382517,1790318633,{"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":145},2336474466412,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","cells  \nReview  \nMolecular Mechanisms of Colorectal Liver Metastases  \nDiamantis I. Tsilimigras 1,*, Ioannis Ntanasis-Stathopoulos 2 and Timothy M. Pawlik 1, *  \nCitation: Tsilimigras, D.I.; Ntanasis-Stathopoulos, I.; Pawlik, T.M. Molecular Mechanisms of Colorectal Liver Metastases. Cells 2023, 12, 1657. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/cells12121657](10.3390/cells12121657)  \nAcademic Editor: Kermit  \nL. Carraway  \nReceived: 25 May 2023  \nRevised: 13 June 2023  \nAccepted: 15 June 2023  \nPublished: 18 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, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 395 W. 12th Ave., Columbus, OH 43210, USA  \n2 Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; [johnntanasis@gmail.com](johnntanasis@gmail.com)  \n* Correspondence: [diamantis.tsilimigras@osumc.edu](diamantis.tsilimigras@osumc.edu) (D.I.T.); [tim.pawlik@osumc.edu](tim.pawlik@osumc.edu) (T.M.P.); Tel.: +614-293-8701 (T.M.P.); Fax: +614-293-4063 (T.M.P.)  \nAbstract: The liver is the most frequently target for metastasis among patients with colorectal cancer mainly because of the portal vein circulation that directly connects the colon and rectum with the liver. The liver tumor microenvironment consists of different cell types each with unique characteristics and functions that modulate the antigen recognition and immune system activation. Primary tumors from other sites “prime” the liver prior to the seeding of cancer cells, creating a pre-metastatic niche. Following invasion into the liver, four different phases are key to the development of liver metastases: a microvascular phase in which cancer cells infiltrate and become trapped in sinusoidal vessels; an extravascular, pre-angiogenic phase; an angiogenic phase that supplies oxygen and nutrients to cancer cells; and a growth phase in which metastatic cells multiply and enlarge to form detectable tumors. Exosomes carry proteins, lipids, as well as genetic information that can create a pre-metastatic niche in distant sites, including the liver. The complexity of angiogenic mechanisms and the exploitation of the vasculature in situ by cancer cells have limited the efficacy of currently available anti-angiogenic therapies. Delineating the molecular mechanisms implicated in colorectal liver metastases is crucial to understand and predict tumor progression; the development of distant metastases; and resistance to chemotherapy, immunotherapy, and targeted treatment.  \nKeywords: CRLM; cells; tumor microenvironment  \n1. Introduction  \nColorectal cancer (CRC) is one of the three most common cancers worldwide. According to the American Cancer Society, approximately 153,000 individuals will be diagnosed with CRC and 52,500 will die from the disease in the United States in 2023 [1] . Despite advances in treatment of patients with CRC, up to 50% will develop colorectal liver metastases (CRLM) during the course of their disease [2–4] . The liver is the most frequent location for metastasis among patients with CRC mainly because of the portal vein system that drains the colon and rectum through the liver. In turn, CRLM remains the main cause of death among patients with CRC [4] .  \nResection and chemotherapy are the mainstay of treatment for patients with CRLM. Nevertheless, only 10–20% of CRLM cases are amenable to resection at the time of diagnosis [5] . Among patients with resectable disease, 5-year post-resection survival ranges between 20–50% and is de","cbCaim5aLCseKWI9","https://ap.wps.com/l/cbCaim5aLCseKWI9","pdf",1388988,13,"English","# Abstract\n# Introduction\n# Molecular Mechanisms of Liver Metastases","[{\"question\":\"Why does colorectal cancer often metastasize to the liver?\",\"answer\":\"Because portal vein circulation directly connects the colon and rectum to the liver, making the liver the most frequent target site for metastasis.\"},{\"question\":\"What are the key phases in liver metastasis development?\",\"answer\":\"The process is described in four phases: a microvascular trapping phase, an extravascular pre-angiogenic phase, an angiogenic phase, and a growth phase where metastatic cells enlarge into detectable tumors.\"},{\"question\":\"How do exosomes influence colorectal liver metastases?\",\"answer\":\"Exosomes transport proteins, lipids, and genetic information that can create a pre-metastatic niche in distant sites, including the liver.\"}]","Molecular Mechanisms of Colorectal Liver Metastases | PDF",1790250849,33]