{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T03:52:42Z","timestamp":1790826762471,"version":"4.1.0"},"reference-count":113,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,18]],"date-time":"2023-06-18T00:00:00Z","timestamp":1687046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 \u201cprime\u201d 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.<\/jats:p>","DOI":"10.3390\/cells12121657","type":"journal-article","created":{"date-parts":[[2023,6,19]],"date-time":"2023-06-19T01:31:14Z","timestamp":1687138274000},"page":"1657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Molecular Mechanisms of Colorectal Liver Metastases"],"prefix":"10.3390","volume":"12","author":[{"given":"Diamantis I.","family":"Tsilimigras","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6328-9783","authenticated-orcid":false,"given":"Ioannis","family":"Ntanasis-Stathopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-9870","authenticated-orcid":false,"given":"Timothy M.","family":"Pawlik","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.3322\/caac.21772","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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