Thus, our data suggest important roles for basigin-2 in lung cancer-induced osteolytic lesion and implicate this protein potential application as a target for lung cancer bone metastasis therapy. Conclusionsīasigin-2 upregulated by RANKL induces MMPs and VEGF, which may increase lung cancer cell metastasis ability and support osteoclastic activity.
Our results indicated the RANKL, pivotal for the control of bone resorption, could increase basigin-2 and its downstream molecules MMP-2, MMP-9 and VEGF expression in vitro. Furthermore, we explored the enhanced basigin-2 molecular mechanism in lung cancer bone metastasis. The lung cancer cells overexpressing basigin-2 strongly induced the osteolytic lesions in immunodeficient mice, which were reduced by treatment with basigin-2 blocking antibody. Then, we demonstrated that basigin-2 could promote lung cancer cells invasion, metastasis and proliferation through upregulating metalloproteinases-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression. We found that basigin-2 was highly expressed in lung cancer bone metastases.
The regulation role of receptor activator of NF-κB ligand (RANKL) on basigin-2 and its downstream molecules were measured by real-time quantitative RT-PCR, gelatin zymography and western blot analysis. The osteoclastic activity of basigin-2 was detected in tibia cancer model by injected of lung cancer cells. Invasion assay and MTT proliferation assay were performed to test the invasion and proliferation of lung cancer cell after modulated basigin-2 expression. Methodsīasigin-2 expression was evaluated in biopsy tissue specimens of 20 lung cancer patients with bone metastases via immunohistochemistry. But little is known about the role of basigin-2 in lung cancer bone metastasis and osteolytic lesion. Basigin-2, a novel cancer-associated biomarker, is upregulated in lung cancer and has been linked with tumor progression. Lung cancer bone metastasis causes poor prognosis.