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Placental growth factor signaling regulates isoform splicing of vascular endothelial growth factor A in the control of lung cancer cell metastasis

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Abstract

Vascular endothelial growth factor (VEGF) family members play critical and complex roles in the regulation of cancer vascularization and metastasis. The exact molecular control of lung cancer metastasis by VEGF family members is not completely understood. Here, we showed that specimens from non-small cell lung cancer (NSCLC) contained significantly higher levels of placental growth factor (PlGF) than paired non-cancer tissue (p < 0.05, N = 25). Moreover, higher levels of PlGF were detected in NSCLC specimens from the patients who had distal metastases than those who had not. High-PlGF levels appeared to be associated with poor patient survival. In vitro, PlGF dose-dependently increased the ratio of pro-angiogenic VEGF isoform (VEGF165) versus anti-angiogenic VEGF isoform (VEGF165b), seemingly through induction of expression of splicing regulatory factor SRp40, resulting in the enhancement of the cancer cell metastatic potential. Higher levels of SRp40 were detected in NSCLC specimens, compared to paired non-cancer tissue (p < 0.05, N = 25). Finally, a strong correlation was detected between the levels of PlGF and SRp40 in NSCLC specimens (r = 0.83, p < 0.0001, N = 25). Together, these data suggest that PlGF may increase NSCLC metastasis through SRp40-mediated mRNA splicing of VEGF.

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Authors and Affiliations

  1. Department of Respiratory Medicine, First Affiliated Hospital of China Medical University, 155 Nanjing North Street, Shenyang, 110001, China

    Zanfeng Wang & Tingwei Liu

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  1. Zanfeng Wang
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  2. Tingwei Liu
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Correspondence to Zanfeng Wang.

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The authors have declared that no competing interests exist.

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All experimental methods and protocols were approved by the Institutional Research Ethics Committee of First Affiliated Hospital of China Medical University.

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Wang, Z., Liu, T. Placental growth factor signaling regulates isoform splicing of vascular endothelial growth factor A in the control of lung cancer cell metastasis. Mol Cell Biochem 439, 163–169 (2018). https://doi.org/10.1007/s11010-017-3145-3

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  • DOI: https://doi.org/10.1007/s11010-017-3145-3

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