Integrins: A Method of Early Intervention in the Treatment of Colorectal Liver Metastases

Abstract

The integrin family of cell surface receptors were principally thought to be involved in cell adhesion. Intense study has shown that these glycoproteins also regulate a diverse range of physiological processes. Inappropriate activation of integrins has been implicated in many pathological processes. Recent studies have shown that these molecules play a key role in the early stages of liver metastasis in colorectal cancer. In vivo experiments have demonstrated that integrins are involved in tumour cell targeting, arrest, adhesion and migration within the hepatic microcirculation. Indeed functional blocking of specific integrins has been shown to significantly impair these early stages of metastasis development. This review examines the current knowledge of integrin participation in this area and highlights the future therapeutic implications. Future targeted therapy against specific integrins would allow not only functional blocking but would provide the potential to deliver specific anti-cancer therapy.

Integrin β3 down-regulates invasive features of ovarian cancer cells in SKOV3 cell subclones

“…A cell phenotype that results from malignant transformation may contain several alterations in cell adhesion receptors. Altered expression of various integrins during tumor growth and progression has been described (Robertson et al 2008;Grzesiak et al 2007;D'Abaco and Kaye 2007;Le Tourneau et al 2007). There are two reports that describe quite opposite opinions about integrin 3.…”

Functional blocking of specific integrins inhibit colonic cancer migration

“…The role of integrin subunits in cancer cell migration is less clear [15]. At least three distinct mechanisms of action have been proposed-direct involvement as seen in endothelial cells [32]; modification of cancer cell phenotype as seen in experiments on prostate cancer [33,34] and colorectal cancer [35,36] or enzymatic recruitment and regulation of expression as shown in breast cancer [37], colorectal cancer [36,38] and melanoma cells [39].…”

“…Recent research suggests that the integrins play a key role in many of the above processes [10][11][12][13][14][15]. This paper examines the key roles that specific integrins play in colonic cancer migration and how these molecules may enable more specific anti-cancer therapies to be developed.…”