2. Academic Validation
  3. Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer

Tumor-derived HMGB1 induces CD62Ldim neutrophil polarization and promotes lung metastasis in triple-negative breast cancer

  • Oncogenesis. 2020 Sep 17;9(9):82. doi: 10.1038/s41389-020-00267-x.
Zhen Wang  # 1 2 3,  Chenghui Yang  # 1 2 3,  Lili Li 1 2 4,  Xiaoyan Jin 1 5,  Zhigang Zhang 1 6,  Haiyan Zheng 3,  Jun Pan 1 2 3,  Liyun Shi 7,  Zhou Jiang 1 2 3,  Ke Su 1 2 3,  Baizhou Li 8,  Xuan Shao 3,  Fuming Qiu 4,  Jun Yan 9,  Jian Huang 10 11 12
Affiliations

Affiliations

  • 1 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 2 Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 3 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 4 Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 5 Department of Surgical Oncology, Zhejiang Taizhou Municipal Hospital, Taizhou, 318008, China.
  • 6 Department of Gynecology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 7 Department of Immunology and Medical Microbiology, Nanjing University of Chinese Medicine, Nanjing, China.
  • 8 Department of Pathology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 9 Department of Medicine and Department of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
  • 10 Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. drhuangjian@zju.edu.cn.
  • 11 Cancer Institute, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. drhuangjian@zju.edu.cn.
  • 12 Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China. drhuangjian@zju.edu.cn.
  • # Contributed equally.
PMID: 32943604 DOI: 10.1038/s41389-020-00267-x
Abstract

Triple-negative breast Cancer (TNBC) is highly aggressive, difficult to treat and commonly develops visceral metastasis, including lung metastasis. We observed that High mobility group box 1 protein (HMGB1) was highly expressed in human TNBC and positively correlated with Cancer metastasis. The hypoxic tumor environment is known to regulate HMGB1 secretion, but an understanding of the underlying mechanism by which tumor-derived HMGB1 regulates interstitial components and promotes breast Cancer lung metastasis has remained elusive. The results of the present study showed that the number of CD62Ldim neutrophils, which have a strong ability to produce neutrophil extracellular traps (NETs), increased significantly in both peripheral blood and lung tissues in a mouse TNBC model and were regulated by tumor-derived HMGB1 through the TLR2 pathway. Furthermore, serum HMGB1 levels were positively correlated with CD62Ldim neutrophils in 86 breast Cancer patients. We demonstrated that CD62Ldim neutrophils accelerated lung metastasis and that interventions targeting the "HMGB1-CD62Ldim neutrophil-NETs" axis could inhibit lung metastasis. Our results suggest that the combination of HMGB1 and CD62Ldim neutrophils is a potential marker for breast Cancer lung metastasis and is novel target for future prevention and therapy.

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