肿瘤相关巨噬细胞来源的 CCL18 通过 PITPNM3 促进乳腺癌转移。
CCL18 from tumor-associated macrophages promotes breast cancer metastasis via PITPNM3.
机构信息
Breast Tumor Center, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University, Guangzhou, China.
出版信息
Cancer Cell. 2011 Apr 12;19(4):541-55. doi: 10.1016/j.ccr.2011.02.006.
Abstract
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.
摘要
肿瘤相关巨噬细胞（TAMs）可以影响癌症的进展和转移，但具体机制尚不清楚。在这里，我们发现乳腺癌 TAMs 大量产生 CCL18，其在血液或肿瘤基质中的表达与转移和患者生存时间缩短有关。乳腺癌 TAMs 释放的 CCL18 通过触发整合素聚集并增强其与细胞外基质的黏附，促进癌细胞的侵袭。此外，我们确定 PITPNM3 是 CCL18 的功能受体，它介导 CCL18 的作用并激活细胞内钙信号。CCL18 促进乳腺癌异种移植物的侵袭和转移，而抑制 PITPNM3 则消除了这些作用。这些发现表明，TAMs 衍生的 CCL18 通过其受体 PITPNM3 在促进乳腺癌转移中发挥关键作用。
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本文引用的文献
1
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Trends Mol Med. 2010 Mar;16(3):133-44. doi: 10.1016/j.molmed.2010.01.003. Epub 2010 Feb 15.
2
Macrophages, innate immunity and cancer: balance, tolerance, and diversity.巨噬细胞、先天免疫与癌症：平衡、耐受与多样性。
Curr Opin Immunol. 2010 Apr;22(2):231-7. doi: 10.1016/j.coi.2010.01.009. Epub 2010 Feb 9.
3
Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development.自分泌 VEGF 信号与肿瘤细胞中的 EGFR 协同作用，促进上皮性癌症的发展。
Cell. 2010 Jan 22;140(2):268-79. doi: 10.1016/j.cell.2009.12.046.
4
Nuclear factor-kappaB and tumor-associated macrophages.核因子-κB 与肿瘤相关巨噬细胞。
Clin Cancer Res. 2010 Feb 1;16(3):784-9. doi: 10.1158/1078-0432.CCR-09-1015. Epub 2010 Jan 26.
5
IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion.IL-4 诱导肿瘤相关巨噬细胞中的组织蛋白酶蛋白酶活性，从而促进癌症生长和侵袭。
Genes Dev. 2010 Feb 1;24(3):241-55. doi: 10.1101/gad.1874010. Epub 2010 Jan 15.
6
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Neuroscience. 2010 Feb 17;165(4):1233-43. doi: 10.1016/j.neuroscience.2009.11.050. Epub 2009 Dec 1.
7
Epithelial-mesenchymal transitions in development and disease.发育与疾病中的上皮-间质转化
Cell. 2009 Nov 25;139(5):871-90. doi: 10.1016/j.cell.2009.11.007.
8
Clinical utility of circulating matrix metalloproteinase-7 (MMP-7), CC chemokine ligand 18 (CCL18) and CC chemokine ligand 11 (CCL11) as markers for diagnosis of epithelial ovarian cancer.循环基质金属蛋白酶-7（MMP-7）、CC 趋化因子配体 18（CCL18）和 CC 趋化因子配体 11（CCL11）作为上皮性卵巢癌诊断标志物的临床效用。
Med Oncol. 2010 Dec;27(4):1246-53. doi: 10.1007/s12032-009-9366-x. Epub 2009 Nov 24.
9
Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation.肿瘤相关巨噬细胞（TAM）作为癌症相关炎症的主要参与者。
J Leukoc Biol. 2009 Nov;86(5):1065-73. doi: 10.1189/jlb.0609385. Epub 2009 Sep 9.
10
CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.CD4(+) T细胞通过增强巨噬细胞的促肿瘤特性来调节乳腺癌的肺转移。
Cancer Cell. 2009 Aug 4;16(2):91-102. doi: 10.1016/j.ccr.2009.06.018.
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