Proangiogenic TIE2+/CD31+ macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes
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- 作者：Ok-Hee Kim (6)
Gun-Hyung Kang (6)
Hyungjoon Noh (6)
Ji-Young Cha (6)
Ho-Jae Lee (6)
Jeong-Hwan Yoon (1)
Mizuko Mamura (1)
Jeong-Seok Nam (6)
Dae Ho Lee (2)
Young A. Kim (3)
Young Joo Park (4)
Hyeonjin Kim (5)
Byung-Chul Oh (6) - 关键词：breast cancer ; melanoma ; metastasis ; proangiogenic macrophages ; tumor ; associated macrophages
- 刊名：Molecules and Cells
- 出版年：2013
- 出版时间：November 2013
- 年：2013
- 卷：36
- 期：5
- 页码：432-438
- 全文大小：
- 作者单位：Ok-Hee Kim (6)
Gun-Hyung Kang (6)
Hyungjoon Noh (6)
Ji-Young Cha (6)
Ho-Jae Lee (6)
Jeong-Hwan Yoon (1)
Mizuko Mamura (1)
Jeong-Seok Nam (6)
Dae Ho Lee (2)
Young A. Kim (3)
Young Joo Park (4)
Hyeonjin Kim (5)
Byung-Chul Oh (6)
6. Lee Gil Ya Cancer and Diabetes Institute, Gachon University Graduate School of Medicine, Incheon, 406-840, Korea
1. Department of Molecular Pathology, Tokyo Medical University, Tokyo, 160-8402, Japan
2. Department of Internal Medicine, Wonkwang University School of Medicine and Hospital, Iksan, 570-749, Korea
3. Department of Pathology, Boramae Medical Center, Seoul National University College of Medicine, Seoul, 156-707, Korea
4. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, 110-744, Korea
5. Department of Radiology, Seoul National University College of Medicine, Seoul, 110-744, Korea - ISSN：0219-1032
文摘
Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-β as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2+/CD31+ macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2+/CD31+ macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2+/ CD31+ macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.