Abstract |
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.
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Authors | R Daniel Bonfil, Aaron Sabbota, Sanaa Nabha, M Margarida Bernardo, Zhong Dong, Hong Meng, Hamilto Yamamoto, Sreenivasa R Chinni, Int Taek Lim, Mayland Chang, Lusia C Filetti, Shahriar Mobashery, Michael L Cher, Rafael Fridman |
Journal | International journal of cancer
(Int J Cancer)
Vol. 118
Issue 11
Pg. 2721-6
(Jun 01 2006)
ISSN: 0020-7136 [Print] United States |
PMID | 16381009
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Heterocyclic Compounds, 1-Ring
- SB 3CT compound
- Sulfones
- Gelatinases
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Topics |
- Animals
- Bone Neoplasms
(physiopathology, prevention & control, secondary)
- Fibrosarcoma
(pathology)
- Gelatinases
(antagonists & inhibitors, metabolism)
- Heterocyclic Compounds, 1-Ring
(pharmacology)
- Humans
- Immunohistochemistry
- Infusions, Parenteral
- Male
- Mice
- Mice, SCID
- Osteolysis
(prevention & control)
- Prostatic Neoplasms
(pathology)
- Sulfones
(pharmacology)
- Tumor Cells, Cultured
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