Peritumoral administration of GPI-anchored TIMP-1 inhibits colon carcinoma growth in Rag-2 gamma chain-deficient mice.
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.
Raggi
Matthias C
MC
Surgery Clinic, Technical University Munich, Munich, Germany.
Djafarzadeh
Roghieh
R
Muenchmeier
Niklas
N
Hofstetter
Monika
M
Jahn
Birgit
B
Rieth
Nicole
N
Nelson
Peter J
PJ
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000737:chemistry / Q000627:therapeutic use*
D004268:DNA-Binding Proteins; D017261:Glycosylphosphatidylinositols; C499308:Rag2 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9