Van den Eynden, Gert G2; Majeed, Ali W2; Illemann, Martin5; Vermeulen, Peter B2; Bird, Nigel C2; Høyer-Hansen, Gunilla6; Eefsen, Rikke Løvendahl2; Reynolds, Andrew R2; Brodt, Pnina2
1 Høyer-Hansen Group, BRIC Research Groups, BRIC, Københavns Universitet2 unknown3 Engelholm Group, BRIC Research Groups, BRIC, Københavns Universitet4 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet5 Engelholm Group, BRIC Research Groups, BRIC, Københavns Universitet6 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
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 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.
Cancer Research, 2013, Vol 73, Issue 7, p. 2031-43