Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms

Wei Cheng Chen, An Chen Chang, Hsiao Chi Tsai, Po I. Liu, Chang Lun Huang, Jeng Hung Guo, Chun Lin Liu, Ju Fang Liu, Le Huynh Hoai Thuong, Chih Hsin Tang

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)


Bone metastases during lung cancer are common. Bone sialoprotein (BSP), a non-collagenous bone matrix protein, plays important functions in bone mineralization processes and in integrin-mediated cell-matrix interactions. Importantly, BSP induces bone metastasis in lung cancer, but the underlying mechanisms remain unclear. This study therefore sought to determine the intracellular signaling pathways responsible for BSP-induced migration and invasion of lung cancer cells to bone. Analyses of the Kaplan-Meier, TCGA, GEPIA and GENT2 databases revealed that high levels of BSP expression in lung tissue samples were associated with significantly decreased overall survival (hazard ratio = 1.17; p = 0.014) and with a more advanced clinical disease stage (F-value = 2.38, p < 0.05). We also observed that BSP-induced stimulation of matrix metalloproteinase (MMP)-14 promoted lung cancer cell migration and invasion via the PI3K/AKT/AP-1 signaling pathway. Notably, BSP promoted osteoclastogenesis in RAW 264.7 cells exposed to RANKL and BSP neutralizing antibody reduced osteoclast formation in conditioned medium (CM) from lung cancer cell lines. Finally, at 8 weeks after mice were injected with A549 cells or A549 BSP shRNA cells, the findings revealed that the knockdown of BSP expression significantly reduced metastasis to bone. These findings suggest that BSP signaling promotes lung bone metastasis via its direct downstream target gene MMP14, which reveals a novel potential therapeutic target for lung cancer bone metastases.
期刊Biochemical Pharmacology
出版狀態已發佈 - 5月 2023

ASJC Scopus subject areas

  • 生物化學
  • 藥理


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