Tumor Endothelial Marker 8, or TEM8, plays varied roles within the human body. Though not widely known, this protein is gaining recognition for its involvement in various biological processes and diseases. Exploring TEM8 offers insights into how cells interact and how certain pathogens and diseases exert their effects. This knowledge is expanding our understanding of both normal bodily functions and disease progression.
What is TEM8?
TEM8, officially named Anthrax Toxin Receptor 1 (ANTXR1), is a protein on the surface of various cells. It functions as a receptor, binding to specific molecules like a lock and key. This binding initiates signals or allows substances to enter the cell. TEM8 is involved in cell attachment and migration, interacting with extracellular matrix components like type I and gelatin collagen.
The ANTXR1 gene, located on chromosome 2p13.3, provides instructions for producing TEM8. The protein has a predicted molecular weight of approximately 63 kilodaltons. Its structure includes an an extracellular domain containing a metal ion-dependent adhesion site. Different forms of TEM8 can be expressed, contributing to its diverse roles in various tissues.
TEM8 and Anthrax Infection
TEM8 is the primary cellular entry point for the anthrax toxin. The toxin’s protective antigen (PA) component binds specifically to TEM8 on the host cell surface. TEM8 is highly expressed in epithelial cells lining the main entry routes for anthrax, including the lungs, skin, and small intestine.
Following PA binding, cellular proteases cleave the PA molecule on the cell surface. This cleavage is followed by the assembly of multiple PA fragments into a heptameric complex. This complex then captures the other two components of the anthrax toxin, lethal factor (LF) and edema factor (EF). The entire complex is then internalized by the cell through endocytosis.
Once inside the cell, the complex travels to acidic compartments called endosomes, which promote a change in the PA structure, leading to pore formation. This pore allows LF and EF to translocate into the cell’s cytoplasm. Inside the cytoplasm, LF and EF disrupt normal cellular processes, leading to the widespread damage and symptoms characteristic of anthrax disease.
TEM8’s Role in Angiogenesis and Cancer
Beyond its connection to anthrax, TEM8 participates in angiogenesis, the formation of new blood vessels. This process is vital for normal physiological events like wound healing and in disease states. TEM8 promotes the migration and adhesion of endothelial cells, the building blocks of blood vessels. It interacts with extracellular matrix proteins, influencing how these cells organize to form new vessels.
In cancer, TEM8’s involvement in angiogenesis is particularly significant. Tumor cells exploit TEM8 to promote the growth of new blood vessels, which supply the growing tumor with oxygen and nutrients. TEM8 is overexpressed on endothelial cells within tumors and on other stromal cells in the tumor microenvironment, in contrast to its limited expression in healthy tissues. This increased presence makes it a specific marker for tumor-associated vasculature.
TEM8 also directly influences cancer cell behavior, contributing to tumor proliferation, migration, and invasion. Reducing TEM8 expression can decrease cancer cell growth and inhibit tumor angiogenesis, limiting primary tumor expansion and the spread of cancer cells. Overexpression of the gene encoding TEM8 has been linked to more aggressive disease progression and unfavorable outcomes in several solid tumors.
Targeting TEM8 for Health
Understanding TEM8’s dual roles in anthrax infection and cancer has opened avenues for new therapeutic strategies. For anthrax, researchers are exploring ways to block the toxin’s entry by targeting TEM8. This involves developing molecules that bind to TEM8 and prevent the protective antigen from attaching. Such approaches aim to create treatments that interfere with the initial stages of infection.
In cancer, TEM8’s overexpression in tumor vasculature makes it an attractive target for anti-cancer therapies. Strategies focus on inhibiting angiogenesis within tumors by blocking TEM8’s function, thereby starving cancer cells of their blood supply. This approach aims to halt tumor growth and metastasis without widespread damage to healthy tissues, given TEM8’s low expression in normal adult vessels. Researchers are investigating various methods to selectively target TEM8 on tumor-associated cells.
Current research also includes developing antibody-drug conjugates (ADCs) that use TEM8 as a specific delivery system for anti-cancer drugs. These ADCs bind to TEM8 on tumor cells and their surrounding support cells, delivering a potent therapeutic payload directly to the cancerous site. This targeted delivery aims to enhance treatment efficacy while minimizing side effects on healthy cells, representing a promising direction in personalized cancer medicine.