TY - JOUR
T1 - Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis
AU - Sangaletti, Sabina
AU - Di Carlo, Emma
AU - Gariboldi, Silvia
AU - Miotti, Silvia
AU - Cappetti, Barbara
AU - Parenza, Mariella
AU - Rumio, Cristiano
AU - Brekken, Rolf A.
AU - Chiodoni, Claudia
AU - Colombo, Mario P.
PY - 2008/11/1
Y1 - 2008/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-08-1327
DO - 10.1158/0008-5472.CAN-08-1327
M3 - Article
C2 - 18974151
AN - SCOPUS:55349145218
VL - 68
SP - 9050
EP - 9059
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 21
ER -