Fibroblast Growth Factor 2 (FGF2) is a protein that functions as a signaling molecule. It belongs to the fibroblast growth factor family and its primary purpose is to regulate a wide range of cellular activities. FGF2 is produced by many cell types and is found in various tissues, where it influences the behavior of neighboring cells.
FGF2 is not a freely circulating signal in the bloodstream like hormones; instead, it acts locally near the site where it is produced. This localized action allows it to provide specific instructions to targeted cells, guiding processes for the body’s maintenance and development. The molecule exists in several forms found in different parts of the cell, like the cytoplasm and nucleus.
The Biological Role of FGF2
A primary function of FGF2 is its role in angiogenesis, the formation of new blood vessels from pre-existing ones. This process is necessary for tissue growth and injury repair. When a tissue requires more oxygen or nutrients, cells release FGF2, which stimulates the endothelial cells lining nearby blood vessels. This causes the endothelial cells to multiply and migrate, forming new capillary tubes that establish a new blood supply.
FGF2 is also a contributor to wound healing. When tissue is damaged, FGF2 helps orchestrate the repair by stimulating the proliferation of fibroblasts. These cells produce the extracellular matrix and collagen that form the framework of new tissue. Promoting the migration of these and other cells to the injury site accelerates wound closure and regeneration.
FGF2’s influence begins during embryonic development, where it helps guide the formation of structures like the limbs and nervous system. Its signaling is part of the sequence of events ensuring organs develop correctly. After development, FGF2 supports the nervous system by promoting the survival, growth, and maintenance of nerve cells (neurons).
How FGF2 Signals to Cells
FGF2’s action depends on communicating with target cells through specific receptors on the cell surface. Using a “lock and key” analogy, FGF2 is the “key,” and proteins on the cell surface called Fibroblast Growth Factor Receptors (FGFRs) are the “locks.” FGF2 can bind to several of the four main types of these receptors, allowing it to influence a diverse range of cells.
For binding to be effective, a molecule called heparan sulfate is required. Heparan sulfate is present on the surface of most cells and acts as a co-receptor. It holds FGF2 and its receptor together, stabilizing the connection to ensure a specific signal is generated. This co-receptor requirement adds another layer of control to the signaling process.
Once FGF2 binds to its receptor and heparan sulfate, it causes two receptors to pair up in an event called dimerization. This pairing activates the intracellular portion of the receptors, triggering a chain of biochemical signals inside the cell. This cascade relays the message to the nucleus, which responds by altering gene expression. This instructs the cell to perform actions like dividing, migrating, or differentiating.
The Link Between FGF2 and Disease
While FGF2 is necessary for normal functions, its dysregulation is linked to several diseases, particularly cancer. The same processes FGF2 promotes in healthy tissue can be exploited by tumors, which often overproduce FGF2 or stimulate surrounding cells to do so. This excess FGF2 hijacks the body’s angiogenesis process, inducing new blood vessels that supply the tumor with oxygen and nutrients to grow.
This tumor-induced angiogenesis allows a localized tumor to expand and metastasize. The new blood vessels serve as conduits for cancer cells to enter the bloodstream and establish secondary tumors. For this reason, FGF2 signaling contributes to tumor progression in various cancers, including squamous lung cancer.
The molecule’s ability to stimulate cell growth can also lead to fibrotic disorders when its activity is excessive. These conditions involve the overgrowth of fibrous connective tissue, leading to scarring and hardening of tissues. For example, in pulmonary fibrosis, excessive FGF2 signaling contributes to the progressive scarring of lung tissue. It may also be involved in forming keloids, which are raised scars from an aggressive healing response.
Therapeutic and Research Applications
Given its role in tissue repair, a recombinant version of FGF2 is used as a therapeutic agent to accelerate healing. It has shown promise in treating chronic wounds like diabetic ulcers and in promoting the repair of bone fractures and severe burns. In these applications, FGF2 is applied directly to the injury site to stimulate the necessary cellular responses.
In cancer treatment, the goal is to inhibit FGF2’s activity. Since many tumors rely on FGF2 signaling for growth and blood supply, researchers developed drugs to block this pathway. These therapies, known as FGFR inhibitors, prevent FGF2 from binding to its receptors or block the subsequent intracellular signals. This targeted strategy cuts off a tumor’s support system, slowing its growth and spread.
FGF2 is also a tool in regenerative medicine and tissue engineering. Scientists use FGF2 in laboratories to grow cells and tissues for research or future transplantation. It can be used to maintain stem cells in an undifferentiated state or to encourage the formation of specific tissues like cartilage or bone. This application holds potential for growing replacement organs or tissues to treat many medical conditions.