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Tumor Biology

, Volume 35, Issue 3, pp 2175–2186 | Cite as

HMGB1 combining with tumor-associated macrophages enhanced lymphangiogenesis in human epithelial ovarian cancer

  • Wenqi Zhang
  • Jing Tian
  • Quan Hao
Research Article

Abstract

Within tumor microenvironment, high-mobility group box protein 1 (HMGB1) and tumor-associated macrophages (TAMs) are able to influence ovarian cancer development and progression via facilitating tumor lymphatic metastasis. However, little is known about the association between HMGB1 and TAMs on lymphangiogenesis in epithelial ovarian cancer (EOC). To investigate the effect of HMGB1 and TAMs on lymphangiogenesis in EOC, immunohistochemistry was performed to determine the expressions of HMGB1, TAMs, and lymphatic vessel density (LVD) in a total of 108 ovarian tissue specimens. Then, the relationships between HMGB1 or TAMs and LVD were assessed by correlation test. In our in vitro study, TAMs were isolated from ascites of EOC patients. Effects of HMGB1, TAMs, and HMGB1 combining with TAMs on lymphatic endothelial cell (LEC) proliferation, migration, and the capillary-like tube formation were measured. Results showed that the expression of HMGB1 and the number of TAMs infiltration were overexpressed in malignant ovarian tumors compared with that in normal ovarian and were closely associated with lymph node metastasis. Positive correlations existed between HMGB1 expression or TAMs count and LVD determination. In an in vitro study, data demonstrated that either HMGB1 or TAMs could facilitate lymphangiogenesis by inducing LEC proliferation, migration, and capillary-like tube formation. Meanwhile, HMGB1 combining with TAMs may augment the pro-lymphangiogenic property. Our data suggest that either HMGB1 or TAMs could facilitate lymphangiogenesis, while HMGB1 coculture with TAMs may strengthen the pro-lymphangiogenic potential, which may serve as a therapeutic target for ovarian cancer.

Keywords

High-mobility group box 1 protein Tumor-associated macrophages Ovarian cancer Lymphangiogenesis 

Notes

Acknowledgments

This work was supported by a grant-in-aid for scientific research (12JCYBJC17000) from the Tianjin Municipal Science and Technology Commission.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Gynecologic OncologyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of CancerTianjinChina
  2. 2.Key Laboratory of Cancer Prevention and TherapyTianjinChina

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