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. [Cancer Res 2008;68(21):9050-9]

Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis / S. Sangaletti, E. Di Carlo, S. Gariboldi, S. Miotti, B. Cappetti, M. Parenza, C. Rumio, R.A. Brekken, C. Chiodoni, M.P. Colombo. - In: CANCER RESEARCH. - ISSN 0008-5472. - 68:21(2008 Nov), pp. 9050-9059. [10.1158/0008-5472.CAN-08-1327]

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

S. Gariboldi;C. Rumio;
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. [Cancer Res 2008;68(21):9050-9]
MATRICELLULAR PROTEIN SPARC ; EPITHELIAL OVARIAN-CANCER ; BREAST-CANCER ; MESENCHYMAL TRANSITION ; ABERRANT METHYLATION ; GROWTH-INHIBITION ; CYSTEINE SPARC ; EXPRESSION ; MIGRATION ; FIBRONECTIN
Settore BIO/16 - Anatomia Umana
nov-2008
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/57390
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