title: High SPARC Expression Starting from Dysplasia, Associated with Breast Carcinoma, Is Predictive for Bone Metastasis without Enhancement of Plasma Levels.
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.
authors.affiliation: Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy. paola.maroni@grupposandonato.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Maroni
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. paola.bendinelli@unimi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Bendinelli
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy. daniele.morelli@istitutotumori.mi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Morelli
authors.affiliation: Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy. lorenzo.drago@unimi.it.|Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. lorenzo.drago@unimi.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Drago
authors.affiliation: Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy. sandroluzzati@tiscali.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Luzzati
authors.affiliation: Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Helth Care (IRCCS), 20161 Milano, Italy. pergiudoc@yahoo.com.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Perrucchini
authors.affiliation: Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy. chiara.bonini@istitutotumori.mi.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonini
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. emanuela.matteucci@unimi.it.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Matteucci
authors.affiliation: Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. a.desiderio@unimi.it.
authors.forename: Maria Alfonsina
authors.initials: MA
authors.lastname: Desiderio
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001859:Bone Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000556:secondary; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D015676:Osteonectin / Q000097:blood / Q000378:metabolism*; D044022:Receptor, Endothelin A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019332:Endothelin-1; D015676:Osteonectin; D044022:Receptor, Endothelin A; C577241:SPARC protein, human
keywords: ETAR; Endothelin 1; SPARC; bone metastasis; breast carcinoma; dysplasia