Therapeutic Effect of Targeted Hyaluronan Binding Peptide on Neurofibromatosis
Abstract
To test our hypothesis that the HA binding peptide (HABP/tachyplesin) may be a new anti-neurofibromatosis agent, we utilized phage display approach to define its binding target. The results demonstrated that 1) HABP/tachyplesin the binds to collagen-like domain of Clq, a key component in the complement pathway; 2) HABP/tachyplesin appears to activate the classical complement cascade, since it triggered several down-stream events including the cleavage and deposition of C4 and C3 and the formation of C5b-9; 3) The HABP/tachyplesin binding to Clq and activation of classical complement cascade can be blocked if the tumor cells are treated with hyaluronidase or a large excess of hyaluronan, indicating that hyaluronan or related glycosarninoglycans were involved in this process; 4) Treatment of tumor cells with HABP/tachyplesin and serum results in an increase in membrane permeability as indicated by the ability of FITC-dextran to enter the cytoplasm; 5) The combination of HABP/tachyplesin and human serum can markedly inhibit the proliferation of tumor cells and this effect is attenuate if the serum is heat-inactivated or if hyaluronidase is added. This represents a new anti-tumor mechanism. We will continue to examine the action mechanism of HABP and-to test if the in vitro anti-tumor effect of HA binding peptide can be translated in vivo against the cell growth of neurofibromatosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA431642
Entities
People
- Charles B. Underhill
- Lurong Zhang
Organizations
- Georgetown University