Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies.

2.50
Hdl Handle:
http://hdl.handle.net/10541/81264
Title:
Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies.
Authors:
Hart, Claire A; Scott, Linda J; Bagley, Steven; Bryden, A A G; Clarke, Noel W ( 0000-0001-7776-8059 ) ; Lang, Shona H
Abstract:
Prostate cancers ability to invade and grow in bone marrow stroma is thought to be due in part to degradative enzymes. The formation of prostate skeletal metastases have been reproduced in vitro by growing co-cultures of prostatic epithelial cells in bone marrow stroma. Expression of urokinase plasminogen activator, matrix metalloproteinase 1 and 7 by prostatic epithelial cells were identified using immunocytochemistry. Also, in vivo tissue sections from human prostatic bone marrow metastases were stained. To establish the role of these enzymes on colony formation, inhibitory antibodies directed against urokinase plasminogen activator, matrix metalloproteinase 1 and matrix metalloproteinase 7 were added into primary prostatic epithelial cells and bone marrow stroma co-cultures. All prostatic epithelial cell cultures stained positively for matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator. Generally prostatic epithelial cells derived from malignant tissues showed increased staining in comparison to epithelia derived from non-malignant tissue. In agreement with in vitro co-cultures, the in vivo tissue sections of prostate bone marrow metastases showed positive staining for all three enzymes. Inhibition studies demonstrated that blocking matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator function reduced the median epithelial colony area significantly in bone marrow stroma co-cultures in vitro. Using a human ex-vivo model we have shown that matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator play an important role in the establishment of prostatic epithelial cells within bone marrow.
Affiliation:
Cancer Research UK - Group of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. chart@picr.man.ac.uk
Citation:
Role of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies. 2002, 86 (7):1136-42 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
8-Apr-2002
URI:
http://hdl.handle.net/10541/81264
DOI:
10.1038/sj.bjc.6600207
PubMed ID:
11953862
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorHart, Claire A-
dc.contributor.authorScott, Linda J-
dc.contributor.authorBagley, Steven-
dc.contributor.authorBryden, A A G-
dc.contributor.authorClarke, Noel W-
dc.contributor.authorLang, Shona H-
dc.date.accessioned2009-09-16T11:29:31Z-
dc.date.available2009-09-16T11:29:31Z-
dc.date.issued2002-04-08-
dc.identifier.citationRole of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies. 2002, 86 (7):1136-42 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid11953862-
dc.identifier.doi10.1038/sj.bjc.6600207-
dc.identifier.urihttp://hdl.handle.net/10541/81264-
dc.description.abstractProstate cancers ability to invade and grow in bone marrow stroma is thought to be due in part to degradative enzymes. The formation of prostate skeletal metastases have been reproduced in vitro by growing co-cultures of prostatic epithelial cells in bone marrow stroma. Expression of urokinase plasminogen activator, matrix metalloproteinase 1 and 7 by prostatic epithelial cells were identified using immunocytochemistry. Also, in vivo tissue sections from human prostatic bone marrow metastases were stained. To establish the role of these enzymes on colony formation, inhibitory antibodies directed against urokinase plasminogen activator, matrix metalloproteinase 1 and matrix metalloproteinase 7 were added into primary prostatic epithelial cells and bone marrow stroma co-cultures. All prostatic epithelial cell cultures stained positively for matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator. Generally prostatic epithelial cells derived from malignant tissues showed increased staining in comparison to epithelia derived from non-malignant tissue. In agreement with in vitro co-cultures, the in vivo tissue sections of prostate bone marrow metastases showed positive staining for all three enzymes. Inhibition studies demonstrated that blocking matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator function reduced the median epithelial colony area significantly in bone marrow stroma co-cultures in vitro. Using a human ex-vivo model we have shown that matrix metalloproteinase 1, matrix metalloproteinase 7 and urokinase plasminogen activator play an important role in the establishment of prostatic epithelial cells within bone marrow.en
dc.language.isoenen
dc.subjectBone Canceren
dc.subjectProstatic Canceren
dc.subjectCancer Metastasisen
dc.subjectCultured Tumour Cellsen
dc.subject.meshAdult-
dc.subject.meshBone Marrow Cells-
dc.subject.meshBone Neoplasms-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMale-
dc.subject.meshMatrix Metalloproteinase 1-
dc.subject.meshMatrix Metalloproteinase 7-
dc.subject.meshNeoplasm Metastasis-
dc.subject.meshProstatic Neoplasms-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUrokinase-Type Plasminogen Activator-
dc.titleRole of proteolytic enzymes in human prostate bone metastasis formation: in vivo and in vitro studies.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK - Group of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. chart@picr.man.ac.uken
dc.identifier.journalBritish Journal of Canceren
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