title: Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.
abstract: Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.
authors.affiliation: Konstantinos A Paschos, Ali W Majeed, Nigel C Bird, Liver Research Group, Department of Oncology, School of Medicine, Royal Hallamshire Hospital, The University of Sheffield, Sheffield S10 2JF, United Kingdom.
authors.forename: Konstantinos A
authors.initials: KA
authors.lastname: Paschos
authors.affiliation: Konstantinos A Paschos, Ali W Majeed, Nigel C Bird, Liver Research Group, Department of Oncology, School of Medicine, Royal Hallamshire Hospital, The University of Sheffield, Sheffield S10 2JF, United Kingdom.
authors.forename: Ali W
authors.initials: AW
authors.lastname: Majeed
authors.affiliation: Konstantinos A Paschos, Ali W Majeed, Nigel C Bird, Liver Research Group, Department of Oncology, School of Medicine, Royal Hallamshire Hospital, The University of Sheffield, Sheffield S10 2JF, United Kingdom.
authors.forename: Nigel C
authors.initials: NC
authors.lastname: Bird
mesh_terms: D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D055166:Hepatic Stellate Cells / Q000166:cytology; D006801:Humans; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000556:secondary*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D016896:Treatment Outcome
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D020782:Matrix Metalloproteinases
keywords: Colorectal cancer; Liver metastasis; Liver sinusoids; Metastatic cascade; Neovascularization
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