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  • Original Article
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Elevated PLGF contributes to small-cell lung cancer brain metastasis

Abstract

Brain metastasis (BM) is a major cause of mortality in small-cell lung cancer (SCLC) patients; however, the molecular pathway of SCLC BM remains largely unknown because of a lack of investigation. Here we screen the levels of some candidate-soluble factors in the serum of SCLC patients and find that SCLC patients with high levels of placental growth factor (PLGF) are prone to BM. Using in vitro blood–brain barrier model, we show that PLGF derived from SCLC cells triggers vascular endothelial growth factor receptor-1-Rho-extracellular regulated protein kinase 1/2 signaling axis activation, results in disassembly of tight junction in brain endothelial cells and promotes SCLC cell transendothelial migration. Furthermore, the downregulation of PLGF suppresses SCLC cell metastasis to the brain in an experimental BM model. These data suggest that PLGF is a potential signature of SCLC BM and a prospective therapeutic target for SCLC BM.

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Acknowledgements

We are grateful to Drs Monique Stins and Kwang Sik Kim (Department of Pediatrics, John Hopkins University School of Medicine) for providing HBMEC and Dr Shuh Narumiya (Kyoto University Faculty of Medicine, Kyoto, Japan) for providing pCAG-myc, pCAG-myc-ROCK-WT and pCAG-myc-ROCK-KDIA. This work was supported by the Trans-Century Training Program Foundation for Talents, Ministry of Education of China (JJH2002–48), the Innovation Team Program Foundation of Liaoning Province (2006T131, LT2011011), the National Natural Science Foundation of China (30600270) and the Science and Technology Foundation of Liaoning Province (20102291).

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Correspondence to Y H Chen.

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Li, B., Wang, C., Zhang, Y. et al. Elevated PLGF contributes to small-cell lung cancer brain metastasis. Oncogene 32, 2952–2962 (2013). https://doi.org/10.1038/onc.2012.313

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