Angiostatin is a proteolytic fragment of plasminogen, a precursor of plasmin, which plays a crucial role in the breakdown of blood clots. Angiostatin specifically inhibits angiogenesis, the process through which new blood vessels form from pre-existing vessels. This property makes it a significant molecule in cancer research, as it can potentially inhibit tumor growth by restricting the blood supply to the tumor.
Angiostatin consists of several kringle domains, which are looped regions stabilized by disulfide bonds. The human recombinant Angiostatin Kringles 1-3 (Ang K1-3) contains the first three kringle structures of plasminogen. These kringle domains are essential for its anti-angiogenic activity. The recombinant form is produced in various expression systems, including E. coli and Pichia pastoris, and is typically a non-glycosylated polypeptide chain with a molecular mass of approximately 30 kDa .
Angiostatin Kringles 1-3 is a potent inhibitor of endothelial cell proliferation, which is a critical step in angiogenesis. By inhibiting the growth of endothelial cells, Ang K1-3 effectively reduces the formation of new blood vessels. This inhibition is more pronounced in Ang K1-3 compared to other kringle combinations, such as Kringles 1-4 .
The anti-angiogenic activity of Angiostatin is mediated through its interaction with various cell surface receptors on endothelial cells. These interactions lead to the inhibition of several signaling pathways that are essential for cell proliferation, migration, and survival. The exact molecular mechanisms are still under investigation, but it is known that Angiostatin can induce apoptosis (programmed cell death) in endothelial cells, further contributing to its anti-angiogenic effects .
Due to its potent anti-angiogenic properties, Angiostatin Kringles 1-3 is extensively studied in cancer research. It has shown promise in preclinical models for inhibiting tumor growth and metastasis. Additionally, Ang K1-3 is being explored for its potential therapeutic applications in other diseases characterized by abnormal angiogenesis, such as diabetic retinopathy and rheumatoid arthritis .
Human recombinant Angiostatin Kringles 1-3 is produced using recombinant DNA technology. The protein is expressed in microbial systems, purified through chromatographic techniques, and lyophilized for storage. It is recommended to store the lyophilized protein at -20°C for long-term use, with the addition of carrier proteins like HSA or BSA to prevent degradation .