What is Immunoglobulin Superfamily?

Immunoglobulin superfamily (IgSF), a superfamily of molecules with domains similar to immunoglobulin in their molecular structure, plays a role in cell adhesion. Cell adhesion molecules (CAMs) immunoglobulin superfamily, one of IgSFs, is involved in the maintenance of cell adhesion, polarity and tumor suppression. As a member of IgSFs, CADM2 inhibits glioma tumorigenesis by regulating the cell cycle and the EMT process, suggesting that CADM2 may be a novel potential therapeutic target in human glioma.

Immunoglobulin superfamily is divided into 3 main classes including neural cell adhesions molecules (NCAM), vascular cell adhesions molecules (VCAM) and intercellular adhesion molecules (ICAM).

--NCAM

The NCAM antigen, a cell surface glycoprotein belonging to the immunoglobulin superfamily involved in cell-cell and cell-matrix adhesion, is over-expressed in many tumour types and is considered a tumour associated antigen. NCAM is expressed in several normal tissues, including natural killer (NK) cells, activated T cells, neurons, glial cells, neuroendocrine glands, skeletal muscle cells and cardiomyocytes. It contributes to a number of physiological processes such as embryogenesis and development, neuronal differentiation and synaptic plasticity. In addition, NCAM can mediate homotypic adhesion of NK cells to NCAM positive tumour cell lines and pathogen and tumour-cell recognition.

Fig 1 Schematic illustration of NCAM-140- and NCAM-180-associated signaling complexes at the plasma membrane

--VCAM and ICAM

Cell adhesion molecules (CAMs), including intercellular adhesion molecule 1 (ICAM-1), cadherins, metalloproteinases and proteolytic enzymes, play a key role in the process that consists of tumor cell dissociation from the primary tumor, intravasation, extravasation and proliferation at a distant site. ICAM-1 and VCAM-1 facilitate attachment of tumor cells to vessel walls, migrate through the walls and stimulate angiogenesis thus participating in the metastatic cascade, also promote the growth of the primary tumor and hence contribute to its progression. ICAM-1 and VCAM-1 are present in colorectal, breast and ovarian cancer as well as melanoma and lymphoma.

Fig 2 FAK/AKT pathway mediates the effect of miR-10b/CADM2 in HCC metastasis

The study and understanding of the mechanism of the immunoglobulin superfamily and its relationship with cancer will help us to find the right drug therapeutic targets.