科学家阐明阻断乳腺癌扩散的新机制

  最近，来自爱丁堡大学的研究人员通过研究发现了一种特殊“扳机”可以促进乳腺癌细胞扩散到肺部组织；研究者表示，阻断乳腺癌小鼠机体的特殊信号或许就可以减少肺部组织次级肿瘤的数量，相关研究发表于国际杂志Journal of Experimental Medicine上，该研究或为开发阻断乳腺癌发展的新型疗法提供思路。
  乳腺癌引发的大部分死亡都是因为癌细胞扩散到了机体的其它组织中，而肺部通常是最易受癌细胞“光顾”的器官，研究者在文章中调查了巨噬细胞如何帮助机体免疫细胞免于原发性肿瘤的扩散；此前研究显示，乳腺癌细胞需要巨噬细胞的帮助才可以入侵到肺部组织建立次级肿瘤。
  本文研究中，研究者发现巨噬细胞需要信号分子—炎症趋化因子才可以同乳腺癌细胞交流沟通，当阻断小鼠机体中的这些信号分子时，小鼠肺部组织的刺激肿瘤的数量就会减少三分之二；而阻断信号分子也可以阻断癌细胞从肺部组织进入到血液之中。人类细胞也可以利用炎症趋化因子来进行彼此沟通，因此研究者希望有一天可以将本文的研究结果转化成为新型疗法来帮助阻断乳腺癌的扩散。
  最后研究者Jeffrey Pollard教授表示，我们的研究发现为以靶向作用肿瘤微环境来开发抗肿瘤疗法提供了新的思路，或为有效阻断乳腺癌的致死性扩散和发展提供一定的帮助和思路。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

CCL2-induced chemokine cascade promotes breast cancer metastasis by enhancing retention of metastasis-associated macrophages
Journal of Experimental Medicine    doi: 10.1084/jem.20141836
Takanori Kitamura,1 Bin-Zhi Qian,1 Daniel Soong,1 Luca Cassetta,1 Roy Noy,2 Gaël Sugano,1 Yu Kato,2 Jiufeng Li,2 and Jeffrey W. Pollard1,2
Pulmonary metastasis of breast cancer cells is promoted by a distinct population of macrophages, metastasis-associated macrophages (MAMs), which originate from inflammatory monocytes (IMs) recruited by the CC-chemokine ligand 2 (CCL2). We demonstrate here that, through activation of the CCL2 receptor CCR2, the recruited MAMs secrete another chemokine ligand CCL3. Genetic deletion of CCL3 or its receptor CCR1 in macrophages reduces the number of lung metastasis foci, as well as the number of MAMs accumulated in tumor-challenged lung in mice. Adoptive transfer of WT IMs increases the reduced number of lung metastasis foci in Ccl3 deficient mice. Mechanistically, Ccr1 deficiency prevents MAM retention in the lung by reducing MAM–cancer cell interactions. These findings collectively indicate that the CCL2-triggered chemokine cascade in macrophages promotes metastatic seeding of breast cancer cells thereby amplifying the pathology already extant in the system. These data suggest that inhibition of CCR1, the distal part of this signaling relay, may have a therapeutic impact in metastatic disease with lower toxicity than blocking upstream targets.