PUBLICATION
Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development
- Authors
- Wang, J., Cao, Z., Zhang, X.M., Nakamura, M., Sun, M., Hartman, J., Harris, R.A., Sun, Y., Cao, Y.
- ID
- ZDB-PUB-141211-4
- Date
- 2015
- Source
- Cancer research 75(2): 306-15 (Journal)
- Registered Authors
- Wang, Jian
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Carcinogenesis/pathology*
- Carcinoma, Lewis Lung/pathology
- Cell Line, Tumor
- Disease Models, Animal*
- Female
- Fibrosarcoma/pathology
- Humans
- Interleukin-6/biosynthesis
- Interleukin-6/genetics
- Macrophages/pathology*
- Male
- Mice
- Mice, Inbred C57BL
- Neoplasm Metastasis
- Neoplasms/blood supply
- Neoplasms/pathology*
- Transfection
- Tumor Necrosis Factor-alpha/biosynthesis
- Tumor Necrosis Factor-alpha/genetics
- Zebrafish
- PubMed
- 25492861 Full text @ Cancer Res.
Citation
Wang, J., Cao, Z., Zhang, X.M., Nakamura, M., Sun, M., Hartman, J., Harris, R.A., Sun, Y., Cao, Y. (2015) Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development. Cancer research. 75(2):306-15.
Abstract
Cancer metastasis can occur at early stages of tumor development due to facilitative alterations in the tumor microenvironment. While imaging techniques have considerably improved our understanding of metastasis, early events remain challenging to study due to the small numbers of malignant cells involved which are often undetectable. Using a novel zebrafish model to investigate this process, we discovered that tumor-associated macrophages (TAM) acted to facilitate metastasis by binding tumor cells and mediating their intravasation. Mechanistic investigations revealed that IL-6 and TNF-α promoted the ability of macrophages to mediate this step. M2 macrophages were particularly potent when induced by IL-4, IL-10 and TGF-β. In contrast, IFN-γ-LPS-induced M1 macrophages lacked the capability to function in the same way in the model. Confirming these observations, we found that human TAM isolated from primary breast, lung, colorectal and endometrial cancers exhibited a similar capability in invasion and metastasis. Taken together, our work shows how zebrafish can be used to study how host contributions can facilitate metastasis at its earliest stages, and they reveal a new macrophage-dependent mechanism of metastasis with possible prognostic implications.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping