Specific interaction between chitosan and matrix metalloprotease 2 decreases the invasive activity of human melanoma cells.
The crucial event in metastasis is tumor invasion which in the case of melanoma cells is dependent on matrix metalloprotease 2 (MMP2). Chitosan (MW ca. 5 x 10(5) g mol(-1), degree of acetylation ca. 30%) attenuated the invasive activity of melanoma cells in a cell-based invasion assay and reduced MMP2 activity in the supernatant of melanoma cells. While the expression level of MMP2 was not affected, the amount of MMP2 in the cell supernatant was reduced, indicating a posttranscriptional effect of chitosan on MMP2. Atomic force microscopy revealed a direct molecular interaction between MMP2 and chitosan forming a complex with a diameter of 349.0 +/- 69.06 nm and a height of 26.5 +/- 11.50 nm. Affinity chromatography revealed a high binding-specificity of MMP2 to chitosan, and a colorimetric MMP2 activity assay suggests a noncompetitive inhibition of MMP2 by chitosan. The possible use of chitosan as a new type of MMP2 inhibitor is discussed.
Gorzelanny
Christian
C
Department of Dermatology, University of Münster, von-Esmarch Strasse 58, 48149, Münster, Germany.
Pöppelmann
Birgit
B
Strozyk
Elwira
E
Moerschbacher
Bruno M
BM
Schneider
Stefan W
SW
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D002846:Chromatography, Affinity / Q000379:methods; D004285:Dogs; D005780:Gelatin / Q000737:chemistry; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D012878:Skin Neoplasms / Q000473:pathology
D005780:Gelatin; D048271:Chitosan; D020778:Matrix Metalloproteinase 2