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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-6-18
pubmed:abstractText
The role of urokinase plasminogen activator (uPA) in osteosarcoma is poorly understood. We examined the importance of uPA, its receptor, uPAR, and its inhibitor, PAI-1, in our in vivo model of metastatic osteosarcoma. Rodent osteosarcoma cells (UMR 106-01) were inoculated into the tibia of athymic mice. Animals were sacrificed and autopsied at 4 days to 5 weeks after inoculation. Tibiae and lungs were excised, fixed, and examined histologically and by in situ hybridization. Osteosarcoma development was associated with tibial swelling and lameness, and radiographic changes included osteolysis and new bone formation. Lung metastases developed spontaneously. In the tibial tumors, uPAR mRNA was expressed early (4 days), whereas uPA and PAI-1 mRNA increased as the tumor invaded the surrounding tissue (3 weeks). There was also an increase in the mRNA expression of the osteoblast-related genes, alpha1(I) procollagen and osteopontin, but not matrix Gla protein. Lung metastases also expressed mRNA for the uPA system and the bone-related proteins. We have produced a model of metastatic osteosarcoma, which typifies the characteristics of the human tumor. Our results suggest that the uPA system plays a role in the local aggressiveness and metastasis of osteosarcoma and, in particular, indicates a possible therapeutic role for uPAR antagonists in the treatment of osteosarcoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1654-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11410503-Animals, pubmed-meshheading:11410503-Disease Models, Animal, pubmed-meshheading:11410503-Disease Progression, pubmed-meshheading:11410503-Female, pubmed-meshheading:11410503-In Situ Hybridization, pubmed-meshheading:11410503-Lung, pubmed-meshheading:11410503-Mice, pubmed-meshheading:11410503-Mice, Inbred BALB C, pubmed-meshheading:11410503-Mice, Nude, pubmed-meshheading:11410503-Neoplasm Metastasis, pubmed-meshheading:11410503-Neoplasms, Experimental, pubmed-meshheading:11410503-Osteosarcoma, pubmed-meshheading:11410503-RNA, Messenger, pubmed-meshheading:11410503-Receptors, Cell Surface, pubmed-meshheading:11410503-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:11410503-Tibia, pubmed-meshheading:11410503-Time Factors, pubmed-meshheading:11410503-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model.
pubmed:affiliation
Department of Orthopaedics, University of Melbourne [H. Z.], St. Vincent's Hospital, Melbourne, Victoria 3065, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't