Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis
S Sangaletti, E Di Carlo, S Gariboldi, S Miotti… - Cancer research, 2008 - AACR
S Sangaletti, E Di Carlo, S Gariboldi, S Miotti, B Cappetti, M Parenza, C Rumio, RA Brekken…
Cancer research, 2008•AACROther 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 …
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 …
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 αvβ5 integrin. Indeed, RNA interference knockdown of β5 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. [Cancer Res 2008;68(21):9050–9]
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