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CD105 promotes hepatocarcinoma cell invasion and metastasis through VEGF

Tumor Biology volume 36, pages 737–745 (2015)Cite this article

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality. Tumor neovascularization is necessarily required for tumor progression and metastasis. CD105 and vascular endothelial growth factor (VEGF) have separately been identified as important contributors to angiogenesis; however, it is unclear if these factors interact to promote the progression of HCC. The goal of this study was to determine the interaction between CD105 and VEGF in HCC, using HCC tissue samples and the human HCC cell line SMMC-7721. In a survey of 89 HCC tumor samples, we determined that CD105 and VEGF expressions were positively correlated with each other and expressed at a higher level in tumor cells. Furthermore, the expression of CD105 was closely related to the tumor-node-metastasis (TNM) staging of HCC, degree of tumor differentiation, portal vein invasion, and lymph node metastasis (P < 0.05). Next, we used a lentiviral system to stably overexpress CD105 in SMMC-7721 cells, which was confirmed at the messenger RNA (mRNA) and protein level. We observed that VEGF expression was increased in these cells, as was cell motility and migration, as assessed using a wound healing assay and Transwell chamber system, respectively. Using VEGF small interfering RNA (siRNA), we also demonstrated that elevated VEGF expression is required to promote increased cell motility and migration in CD105-overexpressing cells. In conclusion, we interpret our data to prove that CD105 promotes the invasion and metastases of liver cancer cells by increasing VEGF expression. These results provide a new theoretical and experimental basis for the treatment of liver cancer.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81071955) and the Scientific Research from Educational Department of Liaoning Province, China (No. 2011225019).

Conflicts of interest

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Author information

Affiliations

  1. Department of General Surgery, Affiliated Shengjing Hospital, China Medical University, Shenyang, China

    Yan Li, Dan Liu, Jingang Liu & Hangyu Li

  2. Department of Oncology, Tumour Angiogenesis and Microenvironment Laboratory (TAML), First Affiliated Hospital, Liaoning Medical College, Jinzhou, China

    Zhenhua Zhai

  3. Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, China

    Xinping Zhong

  4. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, China Medical University, Shenyang, China

    Xin Meng

  5. Department of General Surgery, Affiliated Shenzhou Hospital, Shenyang Medical College, Shenyang, China

    Qingquan Yang

  6. Affiliated Shengjing Hospital, China Medical University, Shenyang, 110004, Liaoning Province, China

    Hangyu Li

Authors
  1. Yan Li
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  2. Zhenhua Zhai
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  3. Dan Liu
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  4. Xinping Zhong
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  5. Xin Meng
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  6. Qingquan Yang
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  7. Jingang Liu
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  8. Hangyu Li
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Correspondence to Hangyu Li.

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Li, Y., Zhai, Z., Liu, D. et al. CD105 promotes hepatocarcinoma cell invasion and metastasis through VEGF. Tumor Biol. 36, 737–745 (2015). https://doi.org/10.1007/s13277-014-2686-2

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  • DOI: https://doi.org/10.1007/s13277-014-2686-2

Keywords

  • Hepatocellular carcinoma
  • Angiogenesis
  • Metastasis
  • CD105
  • Vascular endothelial growth factor