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Inhibition of metastasis of oral squamous cell carcinoma by anti-PLGF treatment

  • Research Article
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Tumor Biology

Abstract

Neovascularization plays a critical role in cancer metastasis. However, the molecular mechanism regulating the neovascularization in oral squamous cell carcinoma (OSCC) is poorly understood. Placental growth factor (PLGF) has been known to regulate pathological angiogenesis and has been recently shown to regulate matrix metalloproteinases (MMPs) for extracellular matrix degradation during neovascularization. Here we aimed to examine whether PLGF may regulate MMPs in the metastasis of OSCC. We found that PLGF and MMP9 levels strongly correlated in OSCC in the patients, both increased in the OSCC from the patients with metastasis of the primary OSCC. Thus, we used several human OSCC cell lines to examine the relationship between PLGF and MMP9. We found that overexpression of PLGF in OSCC cells increased expression of MMP9, while inhibition of PLGF in OSCC cells decreased expression of MMP9. However, adaptation of MMP9 levels in OSCC cells did not affect the levels of PLGF. These data suggest that PLGF may regulate MMP9 in OSCC cells, but not vice versa. Moreover, inhibition of ERK1/2, but not inhibition of PI3k or JNK pathways, substantially abolished the effect of PLGF on MMP9, suggesting that PLGF may increase expression of MMP9 via ERK/MAPK signaling pathway. Thus, our data demonstrate that PLGF-induced cancer neovascularization may be partially mediated through its effect on MMP9 activation in OSCC.

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Acknowledgments

This work was supported by The Natural Science Foundation of Beijing City No. 7122161.

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Authors and Affiliations

  1. Chinese PLA General Hospital, Institute of Stomatology, 100853, Beijing, China

    Jingqiu Bu, Fei Chen & Peng Chen

  2. Five-Year of Clinical Medicine 97, The New Campus of China Medical University, No 77 Puhe Road, 110013, Shenyang, China

    Xi Bu

  3. Department of Stomatology, The General Hospital of the Air Force of the Chinese People’s Liberation Army, No 30 Fucheng Road, Haidian District, 100142, Beijing, China

    Bing Liu

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  1. Jingqiu Bu
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  2. Xi Bu
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  4. Fei Chen
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Corresponding author

Correspondence to Peng Chen.

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Supplementary Fig. 1

PLGF regulated MMP9 in OSCC cells. Human OSCC cell lines were transfected with either a PLGF-expressing plasmid (PLGF), or shPLGF, or null plasmid (−). Overexpression of PLGF in OSCC cells increased transcript levels of MMP9, while inhibition of PLGF in OSCC cells decreased transcript levels of MMP9. (PDF 33 kb)

Supplementary Fig. 2

PLGF was not regulated by MMP9. Human OSCC cell lines were transfected with either a MMP9-expressing plasmid (MMP9), or shMMP9, or a control null plasmid (−). Neither overexpression nor inhibition of MMP9 in OSCC cells altered the transcript levels of PLGF. (PDF 33 kb)

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Bu, J., Bu, X., Liu, B. et al. Inhibition of metastasis of oral squamous cell carcinoma by anti-PLGF treatment. Tumor Biol. 36, 2695–2701 (2015). https://doi.org/10.1007/s13277-014-2892-y

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  • DOI: https://doi.org/10.1007/s13277-014-2892-y

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