期刊
INTERNATIONAL JOURNAL OF CANCER
卷 118, 期 11, 页码 2721-2726出版社
WILEY
DOI: 10.1002/ijc.21645
关键词
matrix metalloproteinases; endothelium; NIMP-2; MMP-9; gelatinase inhibitor
类别
资金
- NCI NIH HHS [R01 CA88028, R01 CA100475] Funding Source: Medline
- NIDDK NIH HHS [DK067687] Funding Source: Medline
Metastasis to the bone is a major clinical complication in patients with prostate cancer (PC). However, therapeutic options for treatment of PC bone metastasis are limited. Gelatinases are members of the matrix metalloproteinase (MMP) family and have been shown to play a key role in PC metastasis. Herein, we investigated the effect of SB-3CT, a covalent mechanism-based MMP inhibitor with high selectivity for gelatinases, in an experimental model of PC bone metastases. Intraperitoneal (i.p.) treatment with SB-3CT (50 mg/kg) inhibited intraosseous growth of human PC3 cells within the marrow of human fetal femur fragments previously implanted in SCID mice, as demonstrated by histomorphometry and Ki-67 immunohistochemistry. The anti-osteolytic effect of SB-3CT was confirmed by radiographic images. Treatment with SB-3CT also reduced intratumoral vascular density and bone degradation in the PC3 bone tumors. A direct inhibition of bone marrow endothelial cell invasion and tubule formation in Matrigel by SB-3CT in vitro was also demonstrated. The use of the highly selective gelatinase inhibitors holds the promise of effective intervention of metastases of PC to the bone. (c) 2005 Wiley-Liss, Inc.
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