the Cellular Adhesion of Molecules

Cellular Adhesion Molecules (CAMs)

Cellular adhesion molecules (CAMs) are glycoproteins that serve as the glue between the cell surface and the extracellular matrix (ECM). They also aid in cell signaling and other associations with its surroundings while preserving cell structure. 2014 (Abbas, Lichtman, and Pillai) Selectins, integrins, immunoglobulin superfamily (IgSF), and cadherins are the four main groups of cellular adhesion molecules (CAMs). Selectins are believed to mediate circulating leukocyte adhesion to vascular endothelial cells. Selectins are classified into three groups, with P and E-selectin located on vascular endothelial cells and L-selectin found only on leucocytes. (Abbas, Lichtman, and Pillai 2014) Integrins promote cell-cell adhesion as well as to the extracellular matrix and are also important in cell signaling. Some examples of integrins are LFA-1 (leucocyte function-associated antigen 1) and the VLA-4 (very late antigen 4). (Abbas, Lichtman, and Pillai 2014) The immunoglobulins superfamily (IgSF) is made up of proteins that contain the Ig domain, for example the ICAM-1 and ICAM-2 (intracellular adhesion molecule-1 and 2) and the VCAM-1 (vascular cell adhesion molecule -1). The Ig-SF are largely constitutively expressed but can be induced when vascular endothelium is being targeted by pro-inflammatory cytokines such as tumor necrosis factors (TNF) and interleukins. (Abbas, Lichtman, and Pillai 2014) The cadherins plays a major role in both cell-cell and cell-matrix adhesion. (Abbas, Lichtman, and Pillai 2014)

Constitutive Expression of CAMs

CAMs are constitutively expressed as the body’s mechanism of being prepared and in constant surveillance. However, only when the body is under attack are specific CAMs induced and up-regulated. This is to avoid the body from producing an inflammatory response when not required and to prevent existing tumor cells from using up-regulated CAMs to metastasize as the mechanism for both pathways are similar. (Strell and Entschladen 2008)

Changing Cell Behavior of CAMs

As mentioned above, CAMs mobilize our body’s immune defense system but are also misused by tumor cells in metastasis. (Strell and Entschladen 2008) Therefore, it is necessary for us to change the cell behavior of CAMs that are involved in these pathological pathways. For example, integrins and selectins have been shown to down-regulate when heparin is used to bind to these CAMs, suggesting the potential inhibitory activity in metastasis when CAMs are biologically altered. (Bendas and Borsig 2012)

Role of CAMs in Cancer Metastasis

Aberrant expression of CAMs such as integrins, selectins, and immunoglobulin superfamily (Ig-SF) are known to play a role in the multistep cascade of cancer metastasis. (Bendas and Borsig 2012) For example, apoptotic resistance which is a critical mechanism in tumor cells to prevent itself from programmed cell death is mediated by neural CAMs (nCAM), a subfamily of IgSF. (Wong, Dye and Coombe 2012). The increase of vascular endothelial growth factor (VEGF) secreted by tumor cells induce the production of ICAM-1, V-CAM 1, and integrins which stimulate the process of angiogenesis. (Wong, Dye and Coombe 2012). The tumor cells also target and down-regulate E cadherins allowing tumor cells to break free from its original site to invade local tissues and disseminate through the systemic circulation. (Wong, Dye, and Coombe 2012).

References

Abbas, A.K., Lichtman, A.H., and Pillai, S. (2014). Cellular and Molecular Immunology 8th Edition. Elsevier Saunders.

Bendas, G., and Borsig, L. (2012). Cancer Cell Adhesion and Metastasis: Selectins, Integrins, and the Inhibitory Potential of Heparins. International Journal of Cell Biology, vol. 2012.

Strell, C., and Entschladen, F. (2008). Extravasation of leukocytes in comparison to tumour cells. Cell Communication and Signalling, vol. 6, no 10.

Wong, C.W., Dye, D.E., and Coombe, D.R. (2012). The Role of Immunoglobulin Superfamily Cell Adhesion Molecules in Cancer Metastasis. International Journal of Cell Biology, vol. 2012.