Author/Authors :
Chen، نويسنده , , Jingqi and Yao، نويسنده , , Yandan and Gong، نويسنده , , Chang and Yu، نويسنده , , Fengyan and Su، نويسنده , , Shicheng and Chen، نويسنده , , Jianing and Liu، نويسنده , , Bodu and Deng، نويسنده , , Hui and Wang، نويسنده , , Fengsong and Lin، نويسنده , , Ling-Jiang Yao، نويسنده , , Herui and Su، نويسنده , , Fengxi and Anderson، نويسنده , , Karen S. and Liu، نويسنده , , Qiang and Ewen، نويسنده , , Mark E. and Yao، نويسنده , , Xuebiao and Song، نويسنده , , Erwei، نويسنده ,
Abstract :
Summary
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.
