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Tumor Biology

, Volume 35, Issue 12, pp 12293–12298 | Cite as

The essential roles of CCR7 in epithelial-to-mesenchymal transition induced by hypoxia in epithelial ovarian carcinomas

  • Shaomei Cheng
  • Lin Han
  • Jingyan Guo
  • Qing Yang
  • Jianfang Zhou
  • Xiangshan Yang
Research Article

Abstract

The chemokine receptor CCR7 and its ligands CCL19/21 mediate the tumor mobility, invasion, and metastasis (Wu et al. Curr Pharm Des. 15:742–57, 2009). Hypoxia induced epithelial-to-mesenchymal transition (EMT) to facilitate the tumor biology. Here, we addressed the roles of CCR7 in epithelial ovarian carcinoma tissues and hypoxia-induced serous papillary cystic adenocarcinoma (SKOV-3) EMT. The expression level of CCR7 protein was analyzed by immunohistochemistry in 30 specimens of epithelial ovarian carcinomas. Western blot was used to investigate the expression of hypoxia-induced CCR7, HIF-1α, and EMT markers (N-cadherin, Snail, MMP-9). In addition, wound healing and Transwell assay were introduced to observe the capacity of migration and invasiveness. Our data showed CCR7 expression was observed in 22 cases of tissues and closely associated with lymph node metastasis and FIGO stage (III + IV). At 6, 12, 24, and 36 h following hypoxia, CCR7 and HIF-1α proteins were both obviously upregulated in a time-dependent method, compared with normal oxygen. In vitro, SKOV-3 expressed N-cadherin, Snail, and MMP-9 once either CCL21 stimulation or hypoxia induction, while hypoxia accompanied with CCL21 induction exhibited strongest upregulation of N-cadherin, Snail, and MMP-9 proteins. Besides, wound healing and Transwell assay further identified that hypoxia with CCL21 stimulation can remarkably promote cell migration and invasiveness. Taken together, CCR7 can constitutively express in epithelial ovarian carcinomas and be induced rapidly in response to hypoxia, which indeed participates in EMT development and prompts the cell migration and invasion. Thus, this study suggested that the epithelial ovarian cancer invasion and metastasis can be inhibited by antagonizing CCR7.

Keywords

CCR7 Epithelial ovarian carcinomas Hypoxia EMT 

Notes

Acknowledgments

We greatly thank other members in Yang Lab for valuable suggestions and writing.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shaomei Cheng
    • 1
  • Lin Han
    • 2
  • Jingyan Guo
    • 3
  • Qing Yang
    • 2
  • Jianfang Zhou
    • 2
  • Xiangshan Yang
    • 4
  1. 1.Department of GynecologyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  2. 2.Department of MedicineAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  3. 3.Department of PharmacyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina
  4. 4.Department of PathologyAffiliated Hospital of Shandong Academy of Medical SciencesJinanChina

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