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Int. J. Mol. Sci. 2015, 16(12), 28108-28122; doi:10.3390/ijms161225997

High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

1
Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy
2
Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy
3
Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 24 June 2015 / Revised: 27 July 2015 / Accepted: 3 August 2015 / Published: 26 November 2015
(This article belongs to the Special Issue Molecular Classification of Human Cancer: Diagnosis and Treatment)
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Abstract

In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ETAR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ETAR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ETAR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer. View Full-Text
Keywords: bone metastasis; dysplasia; SPARC; Endothelin 1; ETAR; breast carcinoma bone metastasis; dysplasia; SPARC; Endothelin 1; ETAR; breast carcinoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Maroni, P.; Bendinelli, P.; Morelli, D.; Drago, L.; Luzzati, A.; Perrucchini, G.; Bonini, C.; Matteucci, E.; Desiderio, M.A. High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels. Int. J. Mol. Sci. 2015, 16, 28108-28122.

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