Colorectal polyposis and immune-based therapies: Dysregulation of cell-cell adhesion (Part 2)

In: Colorectal polyposis

7 Sep 2012

Normal colonic epithelial cells are dependent on cell-cell adhesion and survival factors for the inhibition of apoptosis. In colorectal tumourigenesis, cells develop mechanisms to evade control signals and are able to survive despite the loss of cellcell contacts. Overexpression of adhesion molecules and an abnormal enhancement of growth factors may be an indicator of colon tumourigenesis. In a recent study, chronic trinitrobenzene sulfonic acid-induced inflammation of the colon coincided with an increase in production of TNF-a, IL-1, IL-10 and IFN-y, and expression of the adhesion molecules E-selectin, P-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecules (ICAM-1, ICAM-2), focal adhesion kinase (FAK) and a4P7 integrins.

ICAM-2 is of particular interest as an antigen expressed in murine colon cells which enhances leukotactic factor activity-1-independent adhesion of dendritic cells to the colon endothelium, thus increasing the blood supply for tumour angiogenesis . Similarly, FAK is involved in the promotion of cell survival under certain in vitro conditions and is observed to be overexpressed in invasive and metastatic colon cancer cell lines . The oncogenic effects of FAK are hypothesized to result from increased cell migration and increased cell survival under anchorage-independent conditions. In colon cancer cells, elevated levels of the cytokine Src cause the components of adherens junctions, including vinculin, to be redistributed to Src-induced integrin adhesion complexes, which blocks proper assembly of cell-cell contacts. Cytokines that have been found to inhibit cell-cell adhesion in colon tissue include the TH2 cytokines IL-4 and IL-13. Specifically, IL-4 and IL-13 are thought to inhibit cell-cell adhesion by downregulation of the adhesion molecule E-cadherin. You will always find the required amount of cheap ventolin inhalers at the pharmacy that will be happy to take best care of you by offering safe possibility to purchase the drugs you need without any need to get a prescription first or take any other extra steps.


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