Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis.
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.
Sangaletti
Sabina
S
Department of Experimental Oncology, Immunotherapy and Gene Therapy Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Universita degli Studi di Milano, Milan, Italy.
Di Carlo
Emma
E
Gariboldi
Silvia
S
Miotti
Silvia
S
Cappetti
Barbara
B
Parenza
Mariella
M
Rumio
Cristiano
C
Brekken
Rolf A
RA
Chiodoni
Claudia
C
Colombo
Mario P
MP
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D020868:Gene Silencing; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009362:Neoplasm Metastasis; D015676:Osteonectin / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering
D017931:DNA Primers; D005353:Fibronectins; D039641:Integrin beta Chains; D015676:Osteonectin; D034741:RNA, Small Interfering; C084344:integrin beta5