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dc.contributor.author
Parker, B. S.
dc.contributor.author
Ciocca, Daniel Ramon
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dc.contributor.author
Bidwell, B. N.
dc.contributor.author
Gago, Francisco Eduardo
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dc.contributor.author
Fanelli, Mariel Andrea
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dc.contributor.author
George, J.
dc.contributor.author
Slavin, J. L.
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Möller, A.
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Steel, R.
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Pouliot, N.
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Eckhardt, B. L.
dc.contributor.author
Henderson, M. A.
dc.contributor.author
Anderson, R. L.
dc.date.available
2021-04-15T14:17:45Z
dc.date.issued
2008-10
dc.identifier.citation
Parker, B. S.; Ciocca, Daniel Ramon; Bidwell, B. N.; Gago, Francisco Eduardo; Fanelli, Mariel Andrea; et al.; Primary tumour expression of the cysteine cathepsin inhibitor Stefin A inhibits distant metastasis in breast cancer; John Wiley & Sons Ltd; Journal of Pathology; 214; 3; 10-2008; 337-346
dc.identifier.issn
0022-3417
dc.identifier.uri
http://hdl.handle.net/11336/130099
dc.description.abstract
Using the clinically relevant 4T1-derived syngeneic murine model of spontaneous mammary metastasis to bone, we have identified the cysteine cathepsin inhibitor Stefin A as a gene differentially expressed in primary and metastatic mammary tumours. In primary tumours, Stefin A expression correlated inversely with metastatic potential in 4T1-derived lines and was not detected in tumour cells in culture, indicating induction only within the tumour microenvironment. Enforced expression of Stefin A in the highly metastatic 4T1.2 cell line significantly reduced spontaneous bone metastasis following orthotopic injection into the mammary gland. Consistent with the mouse data, Stefin A expression correlated with disease-free survival (absence of distant metastasis) in a cohort of 142 primary tumours from breast cancer patients. This was most significant for patients with invasive ductal carcinoma expressing Stefin A, who were less likely to develop distant metastases (log rank test, p = 0.0075). In a multivariate disease-free survival analysis (Cox proportional hazards model), Stefin A expression remained a significant independent prognostic factor in patients with invasive ductal carcinoma (p = 0.0014), along with grade and progesterone receptor (PR) status. In human lung and bone metastases, we detected irregular Stefin A staining patterns, with expression often localizing to micrometastases (<0.2 mm) in direct contact with the stroma. We propose that Stefin A, as a cysteine cathepsin inhibitor, may be a marker of increased cathepsin activity in metastases. Using immunohistology, the cathepsin inhibitor was detected co-expressed with cathepsin B in lung and bone metastases in both the murine model and human tissues. We conclude that Stefin A expression reduces distant metastasis in breast cancer and propose that this may be due to the inhibition of cysteine cathepsins, such as cathepsin B.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
John Wiley & Sons Ltd
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
BONE METASTASIS
dc.subject
BREAST CANCER
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CYSTEINE CATHEPSINS
dc.subject
STEFIN A
dc.subject.classification
Oncología
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dc.subject.classification
Medicina Clínica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Primary tumour expression of the cysteine cathepsin inhibitor Stefin A inhibits distant metastasis in breast cancer
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-02-03T13:25:39Z
dc.journal.volume
214
dc.journal.number
3
dc.journal.pagination
337-346
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Parker, B. S.. University of Melbourne; Australia
dc.description.fil
Fil: Ciocca, Daniel Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Bidwell, B. N.. University of Melbourne; Australia
dc.description.fil
Fil: Gago, Francisco Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: Fanelli, Mariel Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
dc.description.fil
Fil: George, J.. Peter MacCallum Cancer Centre; Australia
dc.description.fil
Fil: Slavin, J. L.. University of Melbourne; Australia
dc.description.fil
Fil: Möller, A.. Peter MacCallum Cancer; Australia. , University of Melbourne; Australia
dc.description.fil
Fil: Steel, R.. Peter MacCallum Cancer; Australia. University of Melbourne; Australia
dc.description.fil
Fil: Pouliot, N.. Peter MacCallum Cancer; Australia. University of Melbourne; Australia
dc.description.fil
Fil: Eckhardt, B. L.. Peter MacCallum Cancer; Australia. University of Melbourne; Australia
dc.description.fil
Fil: Henderson, M. A.. Peter MacCallum Cancer; Australia
dc.description.fil
Fil: Anderson, R. L.. Peter MacCallum Cancer; Australia. University of Melbourne; Australia
dc.journal.title
Journal of Pathology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/path.2265
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1002/path.2265
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