The immunoglobulin superfamily (IgSF) is a large family of proteins found in the human body. It consists of over than 765 diverse members (Wong, Dye, & Coombe, 2012). They include cell surface glycoproteins, virus receptors, proteins of the T cell receptor complex, and other molecules. All of them are characterized by the presence of immunoglobulin-like domains. Among the members of the IgSF, there are cell adhesion molecules (CAM) which contribute to hemophilic and heterophilic adhesion. For example, activated leukocyte-cell adhesion molecule (ALCAM), melanoma cell adhesion molecule (MCAM), and the neural cell adhesion molecules 1 and 2 (Lajtha, 2007). Due to their adhesive abilities, IgSF CAMs play an essential role in numerous biological processes. Also, some of them are associated with tumorigenesis and metastasis (Wong, Dye, & Coombe, 2012).
In general, cell adhesion molecules (CAMs) are responsible for cell-cell and cell-extracellular matrix (ECM) interactions. They are vital for maintaining tissue integration by mediating cell migration, proliferation, and differentiation (Wong, Dye, & Coombe, 2012). The list of CAMs includes four types of molecules: cadherins, selectins, integrins, and the IgSF. Changes in their expression lead to various negative consequences, including cancer progression. Wong, Dye, and Coombe (2012) note that medical community pays more attention to the role of integrins and cadherins in metastasis, leaving the IgSF behind. Nevertheless, there is evidence that some members of this family (MCAM, L1CAM, NCAM, PECAM-1, ALCAM, and ICAM-1) are involved in the metastatic cascade.
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This process has five steps: the proliferation of primary tumor cells; invasion of local cells; intravasation and dissemination; extravasation; metastatic colonization and proliferation (Mina & Sledge, 2011). According to Wong, Dye, and Coombe’s (2012) findings, IgSf members are involved in each of these steps.
The cell proliferation in the primary tumor starts when cells achieve the apoptotic resistance. It happens due to two factors: the loss of expression of the tumor suppressor p53, and the abnormal expression of CAMs. There is evidence that NCAM, MCAM, and ALCAM may be connected to the gain of apoptotic resistance (Wong, Dye, & Coombe, 2012). Also, some IgSF members are responsible for adhesion of leukocytes to endothelia and migration of endothelial cells.
Studies show that cells of some types of solid tumors migrate in groups. Therefore, these cells remain adhered to each other. Migration in groups increases their chances of surviving the attack of the immune system and other challenges (Wong, Dye, & Coombe, 2012). Also, there is evidence that several members of the IgSF contribute to the directional cell migration and the degradation of the extracellular matrix.
During the dissemination stage, these molecules may protect cells from apoptosis by providing antiapoptotic signals (just like during the phase of proliferation) as well as by activating focal adhesion kinase (FAK). There is evidence that MCAM and L1CAM are capable of doing so.
Wong, Dye, and Coombe (2012) cite numerous articles which claim that MCAM, ALCAM, NCAM, and L1CAM help to form large cell aggregates which are likely to get stuck in small vessels. Therefore, the tumor cells have the increased chances of penetrating the endothelial basement membrane and the ECM.
At the stage of colonization and proliferation, the IgSF members contribute to the survival and successful development of tumor cells. This process is similar to the stage of the proliferation of the primary tumor.
Several reports claim that tumor cells are capable of avoiding getting stuck in lung capillaries due to their abilities to change shape and to adhere to the walls of much larger vessels (Wong, Dye, & Coombe, 2012). This information indicates that the researchers should conduct more studies to determine the role of the IgSF members during the extravasation stage.
- Lajtha, A. (Ed.). (2007). handbook of neurochemistry and molecular neurobiology: Neural protein metabolism and function (Vol. 3). Berlin: Springer Science & Business Media.
- Mina, L.A. & Sledge, G.W. (2011). Rethinking the metastatic cascade as a therapeutic target. Nature Reviews Clinical Oncology, 8, 325-332.
- Wong, C.W., Dye, D.E., & Coombe, D.R. (2012). The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. International Journal of Cell Biology, 2012.
