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首页> 外文期刊>Cancer Cell >CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3.
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CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3.

机译:来自肿瘤相关巨噬细胞的CCL18通过PITPNM3促进乳腺癌转移。

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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.
机译:肿瘤相关巨噬细胞(TAM)可以影响癌症的进展和转移,但机制仍不清楚。在这里,我们显示乳房TAM大量产生CCL18,其在血液或癌基质中的表达与转移和患者生存率降低相关。乳房TAM释放的CCL18通过触发整联蛋白簇集并增强其对细胞外基质的粘附性来促进癌细胞的侵袭性。此外,我们确定PITPNM3作为CCL18的功能受体,介导CCL18的作用并激活细胞内钙信号传导。 CCL18促进乳腺癌异种移植的侵袭和转移,而抑制PITPNM3则消除了这些作用。这些发现表明,源自TAM的CCL18通过其受体PITPNM3在促进乳腺癌转移中起关键作用。

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