Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization

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	Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization
	Yang, M. ; Shao, J-H ; Miao, Y-J ; Cui, W. ; Qi, Y-F ; Han, J-H ; Lin, X. ; Du, J. ; Han JH(韩家淮)
刊名	http://dx.doi.org/10.1038/cdd.2014.45
	2014
关键词	NF-KAPPA-B IMMUNE-RESPONSE CANCER GROWTH PROGRESSION RECEPTOR KINASE INFILTRATION INFLAMMATION EXPRESSION
英文摘要	Chinese Ministry of Science and Technology [2009CB522205]; Chinese High Technology Research and Development Program [2012AA02A201]; National Science Foundation of China [81170120]; Beijing Nova Program [Z121107002512041]; Macrophages are critical immune effector cells of the tumor microenvironment that promote seeding, extravasation and persistent growth of tumor cells in primary tumors and metastatic sites. Tumor progression and metastasis are affected by dynamic changes in the specific phenotypes of macrophage subpopulations; however, the mechanisms by which tumor cells modulate macrophage polarization remain incompletely understood. Caspase recruitment domain-containing protein 9 (CARD9) is a central adaptor protein of innate immune responses to extracellular pathogens. We report that increased CARD9 expression is primarily localized in infiltrated macrophages and significantly associated with advanced histopathologic stage and the presence of metastasis. Using CARD9-deficient (CARD9(-/-)) mice, we show that bone marrow-derived CARD9 promotes liver metastasis of colon carcinoma cells. Mechanistic studies reveal that CARD9 contributes to tumor metastasis by promoting metastasis-associated macrophage polarization through activation of the nuclear factor-kappa B signaling pathway. We further demonstrate that tumor cell-secreted vascular endothelial growth factor facilitates spleen tyrosine kinase activation in macrophages, which is necessary for formation of the CARD9-B-cell lymphoma/leukemia 10-mucosa-associated lymphoid tissue lymphoma translocation protein 1 complex. Taken together, our results indicating that CARD9 is a regulator of metastasis-associated macrophages will lead to new insights into evolution of the microenvironments supporting tumor metastasis, thereby providing targets for anticancer therapies.
语种	英语
出版者	NATURE PUBLISHING GROUP
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90754]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Yang, M.,Shao, J-H,Miao, Y-J,et al. Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization[J]. http://dx.doi.org/10.1038/cdd.2014.45,2014.
APA	Yang, M..,Shao, J-H.,Miao, Y-J.,Cui, W..,Qi, Y-F.,...&韩家淮.(2014).Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization.http://dx.doi.org/10.1038/cdd.2014.45.
MLA	Yang, M.,et al."Tumor cell-activated CARD9 signaling contributes to metastasis-associated macrophage polarization".http://dx.doi.org/10.1038/cdd.2014.45 (2014).