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

International Journal of Molecular Sciences

Paola Maroni³  Paola Bendinelli¹  Daniele Morelli²  Lorenzo Drago³  Alessandro Luzzati³  Giuseppe Perrucchini³  Chiara Bonini²  Emanuela Matteucci¹  Maria Alfonsina Desiderio¹ 

[1] Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy;Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy;Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy;

关键词: bone metastasis;    dysplasia;    SPARC;    Endothelin 1;    ET_AR;    breast carcinoma;   

DOI  :  10.3390/ijms161225997

来源: mdpi

【 摘 要 】

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/ET_AR 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/ET_AR 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/ET_AR 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.