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PMID: 27187355 Published · epublish English Journal Article Review

Cell and Signal Components of the Microenvironment of Bone Metastasis Are Affected by Hypoxia.

International journal of molecular sciences ·Vol. 17 ·No. 5 ·2016-05-11

Bendinelli P, Maroni P, Matteucci E, Desiderio MA

Abstract

Bone metastatic cells release bone microenvironment proteins, such as the matricellular protein SPARC (secreted protein acidic and rich in cysteine), and share a cell signaling typical of the bone metabolism controlled by Runx2. The megakaryocytes in the bone marrow engrafted by the metastases seem to be one of the principal microenvironment sources of the biological stimuli, implicated in the formation of an osteoblastic niche, and affecting metastasis phenotype and colonization. Educated platelets in the circulation might derive from megakaryocytes in bone metastasis. The evaluation of predictive markers in the circulating platelets might be useful for the stratification of patients for therapeutic purposes. The hypoxic environment in bone metastasis is one of the key regulators of the network of the biological soluble and structural components of the matrix. In bone metastatic cells under hypoxia, similar patterns of Runx2 and SPARC are observed, both showing downregulation. Conversely, hypoxia induces Endothelin 1, which upregulates SPARC, and these biological stimuli may be considered prognostic markers of bone metastasis in breast carcinoma patients.

Keywords
HIF-1 bone metastasis hepatocyte growth factor hypoxic microenvironment megakaryocytes secreted protein acidic and rich in cysteine (SPARC)
MeSH Terms
Animals Bone Neoplasms/metabolism,secondary Cell Hypoxia Humans Hypoxia-Inducible Factor 1, alpha Subunit/genetics,metabolism Oxygen/metabolism Signal Transduction Tumor Microenvironment
Chemicals
HIF1A protein, human Hypoxia-Inducible Factor 1, alpha Subunit Oxygen
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bendinelli Paola
Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. paola.bendinelli@unimi.it.
Maroni Paola
Istituto Ortopedico Galeazzi, Scientific Institute for Research, Hospitalization and Health Care (IRCCS), 20161 Milano, Italy. paola.maroni@grupposandonato.it.
Matteucci Emanuela
Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. emanuela.matteucci@unimi.it.
Desiderio Maria Alfonsina
Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Università degli Studi di Milano, 20133 Milano, Italy. a.desiderio@unimi.it.
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Article Info
Journal
International journal of molecular sciences
Abbr.
Int J Mol Sci
ISSN
1422-0067
DOI
10.3390/ijms17050706
Email
paola.bendinelli@unimi.it
paola.maroni@grupposandonato.it
emanuela.matteucci@unimi.it
a.desiderio@unimi.it
Published
2016-05-11
Epub
2016-00-11
Language
English
Region
Switzerland
NLM ID
101092791
PMCID
PMC4881528
Subset
IM
External Links
PubMed source DOI: 10.3390/ijms17050706 PMC Full Text View journal details
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