The CD44 protein is found on the surface of many cells and is classified as a Cluster of Differentiation molecule. This naming system is a method scientists use to identify and categorize molecules on a cell’s exterior. CD44 functions as a receptor, a structure that receives signals from outside the cell and helps it interact with its immediate environment. These interactions influence how cells respond to various stimuli.
The Fundamental Role of CD44
The primary function of CD44 depends on its interaction with a molecule in the cellular environment called hyaluronic acid (HA). This binding process is often compared to a key fitting into a lock; HA acts as the key that, upon connecting with the CD44 receptor, initiates signals into the cell. This signaling can influence a wide range of cellular behaviors, from movement to survival.
CD44 exists in multiple versions, or isoforms. Although they all originate from the same gene, a process of alternative splicing creates different forms of the CD44 protein. This diversity allows CD44 to perform distinct jobs in various cell types. For example, some isoforms are more common on certain immune cells, while others are found on the cells that line tissues, each tailored to a specific function.
Function in Healthy Tissues
In healthy tissues, CD44 is involved in several processes that maintain the body’s normal operations. One of its functions is in the immune system, where it helps guide white blood cells. These immune cells use CD44 to navigate to sites of infection or injury, enabling them to address potential threats and begin healing.
This protein is also involved in wound healing, particularly in the skin. When a wound occurs, CD44 allows skin cells to move and migrate into the damaged area. This cellular movement is a necessary step for closing the wound and regenerating the tissue. The interaction between CD44 and hyaluronic acid is important here, as HA helps create a hydrated environment that facilitates this cell migration.
The Connection to Cancer Progression
The role of CD44 changes significantly in cancer, where it is often linked to more aggressive disease. Scientists use CD44 as a surface marker to identify a subpopulation of tumor cells known as cancer stem cells (CSCs). These CSCs are thought to be responsible for tumor growth, resistance to therapy, and recurrence. They can be compared to a “queen bee” within the tumor, possessing the ability to self-renew and generate the other cancer cells.
CD44 is directly involved in metastasis, which is the spread of cancer from its original location to other parts of the body. Cancer cells can exploit the normal functions of CD44, such as cell adhesion and migration, for their own benefit. High expression of CD44 allows cancer cells to detach from the primary tumor, enter the bloodstream or lymphatic system, and establish new tumors in distant organs. Its interaction with molecules like matrix metalloproteinases (MMPs) can help break down the barriers surrounding a tumor, facilitating this invasive process.
Involvement in Inflammatory Conditions
Beyond its role in normal healing, the functions of CD44 can become dysregulated and contribute to chronic inflammatory and autoimmune diseases. The same mechanisms that guide immune cells to an injury can cause damage when they are improperly activated. In conditions like rheumatoid arthritis, CD44 on immune cells directs them to the joints, where they mistakenly attack the body’s own tissues, leading to persistent inflammation and damage.
This protein’s involvement is also being investigated in other inflammatory disorders, such as multiple sclerosis. In these cases, the signaling pathways activated by CD44 and its binding to hyaluronic acid can promote the release of pro-inflammatory molecules. This sustained inflammatory response contributes to the tissue damage characteristic of these chronic conditions. The specific CD44 isoforms expressed on immune cells can influence the severity and nature of the inflammatory response.
CD44 as a Therapeutic Target
Given its role in both cancer and inflammation, researchers are exploring ways to target the CD44 protein with new drugs. These strategies aim to disrupt the harmful activities of the protein while leaving its necessary functions in healthy tissues as intact as possible.
In cancer treatment, the primary goal is to develop therapies that target the CD44 found on cancer stem cells. By blocking CD44, researchers hope to inhibit tumor growth, prevent metastasis, and overcome resistance to conventional treatments. For inflammatory diseases, the objective is to create treatments that prevent immune cells from using CD44 to damage healthy tissues. These approaches include developing molecules like neutralizing antibodies or small molecules that interfere with the CD44-HA interaction.