{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:11:00Z","timestamp":1790914260156,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,15]],"date-time":"2015-01-15T00:00:00Z","timestamp":1421280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Danish cancer research foundation"},{"name":"Danish Cancer Society"},{"name":"European Community's Seventh Framework Program FP7\/2007-2011","award":["201279"],"award-info":[{"award-number":["201279"]}]},{"name":"The Capital Region of Denmark, Foundation for Health research"},{"name":"The Villum Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Metastatic growth by colorectal cancer cells in the liver requires the ability of the cancer cells to interact with the new microenvironment. This interaction results in three histological growth patterns of liver metastases: desmoplastic, pushing, and replacement. In primary colorectal cancer several proteases, involved in the degradation of extracellular matrix components, are up\u2010regulated. In liver metastases, their expression is growth pattern dependent. Tissue inhibitor of matrix metalloproteinase\u20101 (TIMP\u20101) is a strong prognostic marker in plasma from colorectal cancer patients, with significant higher levels in patients with metastatic disease. We therefore wanted to determine the expression pattern of TIMP\u20101 in primary colorectal cancers and their matching liver metastases. TIMP\u20101 mRNA was primarily seen in \u03b1\u2010smooth\u2010muscle actin (\u03b1\u2010SMA)\u2010positive cells. In all primary tumors and liver metastases with desmoplastic growth pattern, TIMP\u20101 mRNA was primarily found in \u03b1\u2010SMA\u2010positive myofibroblasts located at the invasive front. Some \u03b1\u2010SMA\u2010positive cells with TIMP\u20101 mRNA were located adjacent to CD34\u2010positive endothelial cells, identifying them as pericytes. This indicates that TIMP\u20101 in primary tumors and liver metastases with desmoplastic growth pattern has dual functions; being an MMP\u2010inhibitor at the cancer periphery and involved in tumor\u2010induced angiogenesis in the pericytes. In the liver metastases with pushing or replacement growth patterns, TIMP\u20101 was primarily expressed by activated hepatic stellate cells at the metastasis\/liver parenchyma interface. These cells were located adjacent to CD34\u2010positive endothelial cells, suggesting a function in tumor\u2010induced angiogenesis. We therefore conclude that TIMP\u20101 expression is growth pattern dependent in colorectal cancer liver metastases. \u00a9 2015 The Authors. <jats:italic>Molecular Carcinogenesis<\/jats:italic> published by Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22269","type":"journal-article","created":{"date-parts":[[2015,1,15]],"date-time":"2015-01-15T21:57:32Z","timestamp":1421359052000},"page":"193-208","source":"Crossref","is-referenced-by-count":26,"title":["Tissue inhibitor of matrix metalloproteinase\u20101 expression in colorectal cancer liver metastases is associated with vascular structures"],"prefix":"10.1002","volume":"55","author":[{"given":"Martin","family":"Illemann","sequence":"first","affiliation":[{"name":"The Finsen Laboratory Rigshospitalet Copenhagen Denmark"},{"name":"Biotech Research and Innovation Center (BRIC) University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Helene 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