Tumor Biology

, Volume 37, Issue 1, pp 911–924 | Cite as

In vivo and in vitro effect of hepatocarcinoma lymph node metastasis by upregulation of Annexin A7 and relevant mechanisms

  • Xian-Yan Wang
  • Feng Gao
  • Yu-Rong Sun
  • Lu-Lu Bai
  • Mohammed Mohammed Ibrahim
  • Bo Wang
  • Jian-Wu Tang
Research Article

Abstract

We unveiled the association of Annexin A7 with vascular endothelial growth factor-C (VEGF-C) and the effect of upregulation of Annexin A7 in Hca-F and Hca-P cells on inhibiting hepatocarcinoma (HCC) lymph node metastasis (LNM) in vitro and in vivo. A total of 200 inbred 615 mice were randomly divided into four equal groups inoculated with Hca-F, Hca-P, FAnxa7-upregulated, and PAnxa7-upregulated cells, respectively. The primary tumor, popliteal, inguinal, and iliac lymph nodes were prepared for immunohistochemical (IHC) staining, real-time quantitative polymerase chain reaction (qRT-PCR) analysis, Western blot, and hematoxylin-eosin (H&E) staining. There was over 50 % increase both in the number of FAnxa7-upregulated and PAnxa7-upregulated cells migrated through the filter compared to their controls (FAnxa7-control, Hca-F and PAnxa7-control, Hca-P). However, no significant differences were noted in invasion ability between them (all P > 0.05). Tumor lymph vessels were significantly reduced in FAnxa7-upregulated and PAnxa7-upregulated tumors when compared with Hca-F and Hca-P tumors (all P < 0.05). Blood vessel density did not differ significantly between FAnxa7-upregulated and PAnxa7-upregulated tumors and Hca-F and Hca-P tumors. Enzyme-linked immunosorbent assay (ELISA) for VEGF-C showed that upregulating Annexin A7 decreased VEGF-C secretion in FAnxa7-upregulated and PAnxa7-upregulated cells (P < 0.05). The IHC staining result showed that the level of serum Annexin A7 was found to be statistically higher in all experimental groups than that in the control group (P < 0.05). The present results indicated that alterations in serum Annexin A7 expression may be of prognostic relevance in HCC lymphatic metastasis.

Keywords

Hepatocarcinoma Annexin A7 Vascular endothelial growth factor-C Lymph node metastasis 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (nos. 30772468 and 81071725) and the Educational Department of Liaoning Province (nos. 2008225010-3, 2007-T024, and 2009S028). This study was also supported by the Key Laboratory of Tumor Metastasis of Liaoning Province.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xian-Yan Wang
    • 1
  • Feng Gao
    • 2
  • Yu-Rong Sun
    • 1
  • Lu-Lu Bai
    • 3
  • Mohammed Mohammed Ibrahim
    • 3
  • Bo Wang
    • 3
  • Jian-Wu Tang
    • 3
  1. 1.Department of PathologyQiqihar Medical UniversityQiqiharPeople’s Republic of China
  2. 2.Department of AnesthesiaThe Third Affiliated Hospital of Qiqihar Medical UniversityQiqiharPeople’s Republic of China
  3. 3.Key Laboratory of Tumor Metastasis of Liaoning Province, Department of PathologyDalian Medical UniversityDalianPeople’s Republic of China

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