Peritumoral administration of GPI-anchored TIMP-1 inhibits colon carcinoma growth in Rag-2 γ chain-deficient mice

Abstract

Abstract Exogenous application of recombinant TIMP-1 protein modified by addition of a glycosylphosphatidylinositol (GPI) anchor allows efficient insertion of the fusion protein into cell membranes. This ‘cell surface engineering’ leads to changes in the proteolytic environment. TIMP-1-GPI shows enhanced as well as novel in vitro biological activities including suppression of proliferation, reduced migration, and inhibition of invasion of the colon carcinoma cell line SW480. Treatment of SW480 tumors implanted in Rag (-/-) common γ chain (-/-) C57BL/6 mice with peritumorally applied TIMP-1-GPI, control rhTIMP-1 protein, or vehicle shows that TIMP-1-GPI leads to a significant reduction in tumor growth.