High SPARC expression starting from dysplasia, associated with breast carcinoma, is predictive for bone metastasis without enhancement of plasma levels

Paola Maroni, Paola Bendinelli, Daniele Morelli, Lorenzo Drago, Alessandro Luzzati, Giuseppe Perrucchini, Chiara Bonini, Emanuela Matteucci, Maria Alfonsina Desiderio

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)28108-28122
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume16
Issue number12
DOIs
Publication statusPublished - Nov 26 2015

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Keywords

  • Bone metastasis
  • Breast carcinoma
  • Dysplasia
  • Endothelin 1
  • ETR
  • SPARC

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications

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