CCL18 from Tumor-Associated Macrophages Promotes Breast Cancer Metastasis via PITPNM3

被引:586
作者
Chen, Jingqi [3 ,4 ]
Yao, Yandan [4 ]
Gong, Chang [4 ]
Yu, Fengyan [4 ]
Su, Shicheng [4 ]
Chen, Jianing [4 ]
Liu, Bodu [4 ]
Deng, Hui [1 ,2 ]
Wang, Fengsong [1 ,2 ]
Lin, Ling [4 ]
Yao, Herui [4 ]
Su, Fengxi [4 ]
Anderson, Karen S. [5 ]
Liu, Qiang [4 ,5 ]
Ewen, Mark E. [5 ]
Yao, Xuebiao [1 ,2 ]
Song, Erwei [4 ]
机构
[1] Hefei Natl Lab Phys Sci Nanoscale, Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Hefei 230027, Anhui, Peoples R China
[3] Guangzhou Med Univ, Affiliated Hosp 2, Dept Med Oncol, Guangzhou 510260, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China
[5] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
关键词
ALTERNATIVE ACTIVATION; CHEMOKINE RECEPTORS; CELLS; EXPRESSION; IDENTIFICATION; INFLAMMATION; CARCINOMA; INVASION; FAMILY; GROWTH;
D O I
10.1016/j.ccr.2011.02.006
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor-associated macrophages (TAMs) can influence cancer progression and metastasis, but the mechanism remains unclear. Here, we show that breast TAMs abundantly produce CCL18, and its expression in blood or cancer stroma is associated with metastasis and reduced patient survival. CCL18 released by breast TAMs promotes the invasiveness of cancer cells by triggering integrin clustering and enhancing their adherence to extracellular matrix. Furthermore, we identify PITPNM3 as a functional receptor for CCL18 that mediates CCL18 effect and activates intracellular calcium signaling. CCL18 promotes the invasion and metastasis of breast cancer xenografts, whereas suppressing PITPNM3 abrogates these effects. These findings indicate that CCL18 derived from TAMs plays a critical role in promoting breast cancer metastasis via its receptor, PITPNM3.
引用
收藏
页码:541 / 555
页数:15
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