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Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis.
- Source :
-
Cancer research [Cancer Res] 2008 Nov 01; Vol. 68 (21), pp. 9050-9. - Publication Year :
- 2008
-
Abstract
- Other than genetic imprinting and epithelial to mesenchymal transition, cancer cells need interaction with the nearby stroma toward metastasis. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein known to regulate extracellular matrix (ECM) deposition and cell-ECM interaction. Gene expression profiles associate SPARC to malignant progression. Using reciprocal bone marrow chimeras between SPARC knockout and wild-type mice, we show that SPARC produced by inflammatory cells is necessary for spontaneous, but not experimental, i.v. metastasis. Macrophage-derived SPARC induces cancer cell migration and enhances their migration to other ECM proteins at least through alpha(v)beta(5) integrin. Indeed, RNA interference knockdown of beta(5) integrin expression reduces cell migration in vitro and metastasis in vivo. Together these results show that macrophage-derived SPARC takes part in metastasis, acting at the step of integrin-mediated migration of invasive cells.
- Subjects :
- Animals
Base Sequence
DNA Primers
Fibronectins metabolism
Flow Cytometry
Gene Silencing
Immunohistochemistry
Integrin beta Chains genetics
Mice
Mice, Inbred BALB C
Mice, Knockout
Osteonectin genetics
RNA, Small Interfering
Extracellular Matrix metabolism
Macrophages metabolism
Neoplasm Metastasis
Osteonectin physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 68
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 18974151
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-08-1327