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Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:3.4.21.73 (
urokinase-type plasminogen activator
)
10,685
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
urokinase plasminogen activator
(
uPA
) system has been widely associated with the development of breast carcinoma. However, the role of the
urokinase
pathway in the development of osseous breast cancer metastases has been largely overlooked. We studied the expression of
uPA
, urokinase plasminogen activator receptor (uPAR)- and plasminogen activator inhibitor type-1 (PAI-1) in human breast carcinomas and their bone metastases, using in situ hybridisation. Studies were performed using paraffin-embedded tissue from 13 ductal carcinomas, 23 invasive ductal carcinomas, five normal breasts and 25 bone metastases. The majority of the tumours examined expressed low to moderate levels of
uPA
mRNA and low to high levels of uPAR and PAI-1 mRNA, which was predominantly localised to the epithelial tumour cells. There was slight over-expression of
uPA
and PAI-1 mRNA and a marked increase in uPAR mRNA expression in the malignant tumours compared with benign tissue. Overall, uPAR and PAI-1 mRNA expression was found to be more variable than
uPA
mRNA, suggesting a possible role of the receptor and inhibitor in the regulation of
uPA
activity. Increased
alpha1(I) procollagen
(COL) and osteopontin (OPN) mRNA expression was detected, primarily in the stromal cells, in malignant tumours compared with the benign tissue. The increased expression of the components of the
uPA
system on the epithelial tumour cells may account for the activation of the proteolytic cascade that occurs during breast cancer metastasis to bone. Furthermore, the over-expression of COL and OPN suggests a possible interaction between these matrix proteins and the
uPA
system.
...
PMID:Urokinase plasminogen activator system gene expression is increased in human breast carcinoma and its bone metastases--a comparison of normal breast tissue, non-invasive and invasive carcinoma and osseous metastases. 1093 85
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.
...
PMID:The expression of the urokinase plasminogen activator system in metastatic murine osteosarcoma: an in vivo mouse model. 1141 May 3
