Cell Adhesion Molecules (CAMs) are proteins found on the surface of cells that mediate binding with other cells or the surrounding environment, a process known as cell adhesion. These molecules function as a form of “molecular glue,” enabling cells to stick to each other and their surroundings. This interaction is fundamental for building and maintaining the complex structures of multicellular organisms. The functions of CAMs are diverse, ranging from maintaining the integrity of tissues to guiding cellular movement and growth.
The Major Families of Cell Adhesion Molecules
Four primary families of CAMs exist: cadherins, integrins, selectins, and the immunoglobulin (Ig) superfamily. Each family has distinct characteristics, and their activity is often categorized by calcium dependence. Cadherins, selectins, and integrins are calcium-dependent, while the Ig superfamily is not.
Cadherins hold cells together within tissues by mediating homophilic binding, where a cadherin on one cell binds to an identical cadherin on a neighbor. This interaction is what gives tissues their structural strength. In contrast, integrins facilitate heterophilic binding, linking cells to the extracellular matrix (ECM)—the network of molecules surrounding cells.
Selectins and the Ig superfamily are also involved in cell-to-cell adhesion. Selectins are known for their role in the immune system, mediating the initial adhesion of white blood cells to blood vessel walls. The Ig superfamily is a diverse group involved in both homophilic and heterophilic binding, contributing to many cellular recognition processes.
Maintaining Tissue Structure and Integrity
A primary function of cell adhesion molecules is providing physical stability to tissues and organs. By anchoring cells to one another and the extracellular matrix, CAMs ensure tissues can withstand mechanical stress and maintain their structure. Without these molecular connections, multicellular life would not be possible.
E-cadherin, a member of the cadherin family found in epithelial tissues like skin, exemplifies this structural role. E-cadherin molecules on one epithelial cell link to E-cadherins on adjacent cells, forming adherens junctions. These junctions act like zippers, fastening cells together to create a continuous barrier.
This connection extends beyond just a surface-level attachment. The intracellular portion of the cadherin molecule connects to the cell’s internal cytoskeleton, specifically to actin filaments. This linkage creates a mechanically coupled network that runs throughout the entire tissue, distributing forces and maintaining architectural integrity. The loss or dysfunction of E-cadherin can compromise this integrity, leading to a breakdown in tissue structure.
Directing Cell Migration
Beyond structural support, cell adhesion molecules are central to cell movement. They act as guideposts, directing cells to their proper locations during processes like embryonic development. CAMs ensure cells migrate to and stop at their correct destinations, which is necessary to form complex tissues and organs.
Leukocyte extravasation, the movement of white blood cells from the bloodstream into tissues to fight infection, illustrates this process. Initially, selectins on the blood vessel wall mediate the capture and “rolling” of leukocytes along the vessel lining. This slows them down from the fast-flowing blood.
Following this initial capture, integrins on the leukocyte surface become activated. These activated integrins bind firmly to Ig superfamily members, such as Intercellular Adhesion Molecule-1 (ICAM-1), on the endothelial cells. This firm adhesion stops the rolling and allows the leukocyte to crawl through gaps between endothelial cells, a process called transmigration, to reach the site of infection.
Transmitting Signals into the Cell
Cell adhesion is also a form of cellular communication. The binding of a CAM to another cell or the extracellular matrix initiates biochemical signals within the cell, a process called “outside-in signaling.” This allows the cell to sense its environment and respond, translating the physical act of adhesion into an internal message that influences cell behavior.
Integrins are prominent in signal transduction. When an integrin binds to an ECM component, its intracellular domain can trigger various signaling pathways. For instance, this binding can activate enzymes like focal adhesion kinase (FAK), which influences a wide range of cellular processes.
These adhesion-mediated signals can impact cellular decisions, such as whether a cell should grow, divide, move, or undergo programmed cell death (apoptosis). For example, most normal cells require attachment to a substrate to survive and proliferate, a phenomenon known as anchorage-dependence. This requirement is enforced by signals from integrin binding, which tells the cell it is in the correct environment.
Consequences of Malfunctioning Cell Adhesion
If cell adhesion processes malfunction, the consequences can lead to various diseases. The dysregulation of CAMs can disrupt tissue structure, interfere with immune responses, and promote disease progression. Understanding these malfunctions provides insight into the mechanisms of several pathological conditions.
Adhesion malfunction is evident in cancer metastasis. In many epithelial cancers, a loss of E-cadherin expression weakens the connections between cancer cells, allowing them to detach from the primary tumor. This enables the cancer cells to invade surrounding tissues and migrate to distant parts of the body to form secondary tumors.
Malfunctioning cell adhesion also contributes to chronic inflammatory diseases like rheumatoid arthritis. In this condition, the overexpression of certain CAMs, such as VCAM-1, on blood vessel walls in the joints leads to excessive recruitment of leukocytes. This sustained influx of immune cells into the joint tissue drives the chronic inflammation and tissue damage characteristic of the disease. Modulating the activity of these adhesion molecules is an active area of therapeutic research for both cancer and inflammatory disorders.