Cell Adhesion Molecules (CAMs) are specialized integral membrane proteins that allow cells to form physical contacts with the extracellular matrix (cell-matrix adhesion) or with neighboring cells (cell-cell adhesion). These molecules are essential for maintaining the structural integrity of tissues, regulating cell growth, and orchestrating complex processes like embryonic development and immune responses.

Classification of CAMs

Based on their structure and chemical requirements, CAMs are broadly classified into several superfamilies:

1. Cadherins: These are calcium ()-dependent glycoproteins. They are primarily involved in cell-cell junctions, such as adhering junctions and desmosomes, where they link the membranes of adjacent cells.

2. Selectins: These molecules are crucial for the initial stages of inflammation. For example, E-selectins and P-selectins on activated endothelial cells allow circulating neutrophils to "roll" along the blood vessel wall.

3. Integrins: These function mainly as matrix receptors, anchoring the intracellular cytoskeleton to the extracellular matrix proteins like fibronectin and laminin. They also play a role in the "firm binding" of white blood cells during their exit from blood vessels into tissues.

4. Immunoglobulin Superfamily (N-CAMs): These are -independent molecules, such as the Neural Cell Adhesion Molecules (N-CAMs) and Intercellular Adhesion Molecules (ICAMs), which participate in the adhesion between neurons and other cell types.

Physiological Functions

• Structural Support and Polarity: CAMs help organize cells into coherent tissues and define distinct domains, such as the apical and basolateral surfaces in epithelial cells.

• Transmembrane Signaling: The binding of a CAM to its ligand can produce conformational changes that are transmitted to the cell interior. These signals can influence cell proliferation, migration, and differentiation.

• Immune Defense (Diapedesis): CAMs coordinate the movement of leukocytes from the blood to the site of infection. This involves a sequence of rolling (via selectins), firm sticking (via integrins and ICAM-1), and exiting the vessel (diapedesis).

• Developmental Guidance: In the developing nervous system, CAMs are expressed sequentially to guide the migration of neurons and the growth of axons toward their correct targets.

Clinical Significance

• Metastasis: A hallmark of metastatic tumor cells is the loss of normal cell-cell and cell-matrix adhesion. For instance, reduced expression of cadherins in epithelial tumors often correlates with the tumor's ability to break away and spread to distant sites in the body.

• Genetic Disorders: Mutations in the components that link the cell membrane to the submembranous cytoskeleton (like ankyrin and spectrin) can lead to fragile red blood cells that are easily destroyed in the circulation.

• Inflammation: Excessive activation of leukocyte adhesion receptors can lead to tissue damage in chronic inflammatory diseases. Conversely, a deficiency in these receptors (Leukocyte Adhesion Deficiency) prevents white blood cells from reaching infected tissues, leading to recurrent bacterial infections