Sangaletti Sabina, Di Carlo Emma, Gariboldi Silvia, Miotti Silvia, Cappetti Barbara, Parenza Mariella, Rumio Cristiano, Brekken Rolf A, Chiodoni Claudia, Colombo Mario P
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.
Cancer Res. 2008 Nov 1;68(21):9050-9. doi: 10.1158/0008-5472.CAN-08-1327.
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.
除了基因印记和上皮-间质转化外，癌细胞还需要与附近的基质相互作用以实现转移。富含半胱氨酸的酸性分泌蛋白（SPARC）是一种基质细胞蛋白，已知其可调节细胞外基质（ECM）沉积和细胞与ECM的相互作用。基因表达谱将SPARC与恶性进展联系起来。利用SPARC基因敲除小鼠和野生型小鼠之间的相互骨髓嵌合体，我们发现炎症细胞产生的SPARC对于自发性静脉转移是必需的，但对于实验性静脉转移则不是必需的。巨噬细胞衍生的SPARC至少通过α(v)β(5)整合素诱导癌细胞迁移并增强其向其他ECM蛋白的迁移。事实上，RNA干扰敲低β(5)整合素表达可减少体外细胞迁移和体内转移。这些结果共同表明，巨噬细胞衍生的SPARC参与转移，作用于整合素介导的侵袭性细胞迁移步骤。
