Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis.

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.

• Authors: Sabina Sangaletti, Emma Di Carlo, Silvia Gariboldi, Silvia Miotti, Barbara Cappetti, Mariella Parenza, Cristiano Rumio, Rolf A Brekken, Claudia Chiodoni, Mario P Colombo
• Journal: Cancer research (Cancer Res) Vol. 68 Issue 21 Pg. 9050-9 (Nov 01 2008) ISSN: 1538-7445 [Electronic] United States
• PMID: 18974151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Fibronectins
• Integrin beta Chains
• Osteonectin
• RNA, Small Interfering
• integrin beta5

Topics

• Animals
• Base Sequence
• DNA Primers
• Extracellular Matrix (metabolism)
• Fibronectins (metabolism)
• Flow Cytometry
• Gene Silencing
• Immunohistochemistry
• Integrin beta Chains (genetics)
• Macrophages (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Neoplasm Metastasis
• Osteonectin (genetics, physiology)
• RNA, Small Interfering