The purpose of this grant proposal is study the mechanism of action of the inhibition of lung tumor colonization in mice produced by a novel protein purified from the salivary gland extract of Haementeria officinalis, the Mexican leech. The protein termed antistasin will further characterized biophysically and biochemically. The molecular weight, carbohydrate composition, amino-acid sequence, and isoelectric point of the purified material will be determined. The effect of this protein will be investigated on the following steps postulated to be involved in the metastatic mechanism: a) fibrin dependent tumor cell adhesion, b) heparin-like dependent tumor cell adhesion to the subendothelial extracellular matrix, and c) tumor cell extravasation dependent on tumor specific Type IV collagenase activity. The immediate goal of these studies is to develop an adjuvant for the treatment of metastasis in mice. In addition, the long-range goals of this research proposal will be to develop the production of antistasin by recombinant DNA technology for preclinical and clinical trials.
| Nutt, E; Gasic, T; Rodkey, J et al. (1988) The amino acid sequence of antistasin. A potent inhibitor of factor Xa reveals a repeated internal structure. J Biol Chem 263:10162-7 |
| Tuszynski, G P; Gasic, T B; Gasic, G J (1987) Isolation and characterization of antistasin. An inhibitor of metastasis and coagulation. J Biol Chem 262:9718-23 |
| Tuszynski, G P; Gasic, T B; Rothman, V L et al. (1987) Thrombospondin, a potentiator of tumor cell metastasis. Cancer Res 47:4130-3 |
| Iwakawa, A; Gasic, T B; Viner, E D et al. (1986) Promotion of lung tumor colonization in mice by the synthetic thrombin inhibitor (no. 805) and its reversal by leech salivary gland extracts. Clin Exp Metastasis 4:205-20 |
