Inhibition of human prostate cancer growth, osteolysis and angiogenesis in a bone metastasis model by a novel mechanism‐based selective gelatinase inhibitor

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. H...

Full description

Saved in:
Bibliographic Details
Published in:International journal of cancer 2006-06, Vol.118 (11), p.2721-2726
Main Authors: Bonfil, R. Daniel, Sabbota, Aaron, Nabha, Sanaa, Bernardo, M. Margarida, Dong, Zhong, Meng, Hong, Yamamoto, Hamilto, Chinni, Sreenivasa R., Lim, Int Taek, Chang, Mayland, Filetti, Lusia C., Mobashery, Shahriar, Cher, Michael L., Fridman, Rafael
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Bone Neoplasms - physiopathology
Bone Neoplasms - prevention & control
Bone Neoplasms - secondary
Chemotherapy
endothelium
Fibrosarcoma - pathology
gelatinase inhibitor
Gelatinases - antagonists & inhibitors
Gelatinases - metabolism
Heterocyclic Compounds, 1-Ring - pharmacology
Humans
Immunohistochemistry
Infusions, Parenteral
Male
matrix metalloproteinases
Medical sciences
Mice
Mice, SCID
MMP‐2
MMP‐9
Osteolysis - prevention & control
Pharmacology. Drug treatments
Prostatic Neoplasms - pathology
Sulfones - pharmacology
Tumor Cells, Cultured
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. © 2005 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.21645