The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells a...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (7), p.2031-2043
Main Authors: VAN DEN EYNDEN, Gert G, MAJEED, Ali W, ILLEMANN, Martin, VERMEULEN, Peter B, BIRD, Nigel C, HØYER-HANSEN, Gunilla, EEFSEN, Rikke Løvendahl, REYNOLDS, Andrew R, BRODT, Pnina
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver Neoplasms - secondary
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Pharmacology. Drug treatments
Tumor Microenvironment
Tumors
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Summary:The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells arriving in the liver via the bloodstream encounter the microenvironment of the hepatic sinusoid. The interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate. The sinusoidal cells can have a dual role, sometimes fatal to the tumor cells but also facilitatory to their survival and growth. Adhesion molecules participate in these interactions and may affect their outcome. Bone marrow-derived cells and chemokines also play a part in the early battle for survival of the metastases. Once the tumor cells have arrested and survived the initial onslaught, tumors can grow within the liver in 3 distinct patterns, reflecting differing host responses, mechanisms of vascularization, and proteolytic activity. This review aims to present current knowledge of the interactions between the host liver cells and the invading metastases that has implications for the clinical course of the disease and the response to treatment.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-12-3931