Megan Emiliani

Introduction. Osteosarcoma (OS) is the most common and malignant primary bone tumor in children and adolescents¹. It originates from mesenchymal stem cells in the bone marrow¹. The leading cause of mortality is metastasis to the lungs². The exact mechanism by which it metastasizes remains unclear. The 5-year overall survival rate for patients with OS is only 60%, and even less at only 20% once it has metastasized³. OS is highly resistant to current chemotherapy and radiation¹. Therefore, there is need for better drugs that prevent metastasis. In this review, we examine studies that target the Wnt/β-catenin signaling pathway to determine its effects on OS cells. β-catenin is highly expressed in OS cells and thought to be involved in progression and metastasis³. Methods. OS cells were extracted from human tumors, and cell lines were cultured⁴. siRNAs were used to knockdown regulators of the Wnt/β-catenin pathway, including RAC2, NRSN2, GLI-2, REGy, and Sox2^4-8. OS cell lines were injected into mice, and tumor growth was measured⁵. Western blot measured expression of proteins involved in the pathway⁶. Flow cytometry detected cell apoptosis⁵. Wound healing assay demonstrated cell migration⁷. Results. Silencing RAC2, an upregulator of Wnt signaling, in OS cells reduced tumor growth and size⁵. There was a positive correlation between NRSN2 and Wnt/β-catenin signaling, and OS tumors were significantly smaller in mice with silenced NRSN2⁴. Knockdown of GLI-2 decreased β-catenin levels and suppressed OS cell proliferation⁶. When REGy was knocked down in OS cells, expression of β-catenin decreased, the percentage of OS cells arrested in G0/G1 phase increased, and the rate of apoptosis increased⁷. Silencing of Sox2, an upregulator of Wnt/β-catenin, led to a significantly reduced OS invasion cell number and lower OS cell migration rates⁸. Conclusions. In these studies, inhibiting Wnt/β-catenin signaling by knocking down various regulators suppressed OS cell proliferation and tumor growth^4-6, induced apoptosis⁷, and reduced migration and invasion⁸. Therefore, drug therapies that target this signaling pathway may improve the treatment of osteosarcoma.

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