SPARCL1 suppresses osteosarcoma metastasis and recruits macrophages by activation of canonical WNT/β-catenin signaling through stabilization of the WNT-receptor complex.

Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that duanyu1842RCL1 inhibits OS metastasis. We further demonstrated that WNT/β-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT-receptor complex stabilization. Activation of WNT/β-catenin signaling contributes to the inhibitory effects on OS metastasis. Furthermore, we uncovered a paracrine effect of duanyu1842RCL1 on macrophage recruitment through activated WNT/β-catenin signaling-mediated secretion of chemokine ligand5 from OS cells. These findings suggest that the targeting of duanyu1842RCL1 as a new anti-metastatic strategy for OS patients.

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