Raggi Matthias C, Djafarzadeh Roghieh, Muenchmeier Niklas, Hofstetter Monika, Jahn Birgit, Rieth Nicole, Nelson Peter J
Surgery Clinic, Technical University Munich, Munich, Germany.
Biol Chem. 2009 Sep;390(9):893-7. doi: 10.1515/BC.2009.098.
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 gamma 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.
通过添加糖基磷脂酰肌醇（GPI）锚修饰的重组TIMP-1蛋白的外源应用能够使融合蛋白有效插入细胞膜。这种“细胞表面工程”导致蛋白水解环境发生变化。TIMP-1-GPI在体外表现出增强的以及新的生物学活性，包括抑制增殖、减少迁移和抑制结肠癌细胞系SW480的侵袭。用瘤周应用的TIMP-1-GPI、对照重组人TIMP-1蛋白或赋形剂处理植入Rag（-/-）共同γ链（-/-）C57BL/6小鼠体内的SW480肿瘤，结果表明TIMP-1-GPI可显著抑制肿瘤生长。
