Selectively desulfated heparin inhibits P-selectin-mediated adhesion of human melanoma cells.
Accumulating evidence has suggested that one of the mechanisms by which heparin inhibits metastasis is by blocking the P-selectin-based interaction of platelets with tumor cells. Here we demonstrate that the sulfate groups at C6/N and especially C6, but not C2 and C3, of heparin play a critical role in P-selectin recognition and that 2-O,3-O-desulfated heparin can block P-selectin-mediated A375 human melanoma cell adhesion. Our findings show that chemical modification of heparin, especially 2-O,3-O-desulfation, may result in a therapeutic agent that is anti-metastatic because it blocks unwanted P-selectin-dependent adhesion but that lacks dose-limiting anticoagulant effects.
Wei
Min
M
Institute of Genetics and Cytology, School of Life Science, Northeast Normal University, Changchun, Jilin 130024, People's Republic of China.
Gao
Yanguang
Y
Tian
Meihong
M
Li
Na
N
Hao
Shui
S
Zeng
Xianlu
X
D000925:Anticoagulants / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology*; D006493:Heparin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000517:prevention & control; D019007:P-Selectin / Q000502:physiology*; D012878:Skin Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000925:Anticoagulants; D019007:P-Selectin; D006493:Heparin