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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Recruitment of a myeloid cell subset (CD11b/Gr1mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis
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Recruitment of a myeloid cell subset (CD11b/Gr1mid) via CCL2/CCR2 promotes the development of colorectal cancer liver metastasis

机译：通过CCL2 / CCR2募集骨髓细胞亚群（CD11b / Gr1mid）促进结直肠癌肝转移的发展

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Liver metastasis from colorectal cancer is a leading cause of cancer mortality. Myeloid cells play pivotal roles in the metastatic process, but their prometastatic functions in liver metastasis remain incompletely understood. To investigate their role, we simulated liver metastasis in C57BL/6 mice through intrasplenic inoculation of MC38 colon carcinoma cells. Among the heterogeneous myeloid infiltrate, we identified a distinct population of CD11b/Gr1mid cells different from other myeloid populations previously associated with liver metastasis. These cells increased in number dramatically during establishment of liver metastases and were recruited from bone marrow by tumor-derived CCL2. Liver metastasis of Lewis lung carcinoma cells followed this pattern but this mechanism is not universal as liver colonization by B16F1 melanoma cells did not recruit similar subsets. Inhibition of CCL2 signaling and absence of its cognate receptor CCR2 reduced CD11b/Gr1mid recruitment and decreased tumor burden. Depletion of the CD11b/Gr1mid subset in a transgenic CD11b-diphtheria toxin receptor mouse model markedly reduced tumor cell proliferation. There was no evidence for involvement of an adaptive immune response in the prometastatic effects of CD11b/Gr1mid cells. Additionally, an analogous myeloid subset was found in liver metastases of some colorectal cancer patients. Conclusion: Collectively, our findings highlight the importance of myeloid cells-in this case a selective CD11b/Gr1mid subset-in sustaining development of colorectal cancer liver metastasis and identify a potential target for antimetastatic therapy.
机译：大肠癌的肝转移是癌症死亡的主要原因。髓样细胞在转移过程中起着关键作用，但它们在肝转移中的前转移功能仍未完全了解。为了研究它们的作用，我们通过脾脏接种MC38结肠癌细胞模拟了C57BL / 6小鼠的肝转移。在异质性髓细胞浸润中，我们鉴定出与先前与肝转移相关的其他髓细胞不同的CD11b / Gr1mid细胞的独特群体。在肝转移建立期间，这些细胞的数量急剧增加，并通过肿瘤来源的CCL2从骨髓中募集。 Lewis肺癌细胞的肝转移遵循这种模式，但这种机制并不普遍，因为B16F1黑色素瘤细胞在肝脏中的定殖没有募集相似的亚群。 CCL2信号的抑制和其相关受体CCR2的缺乏减少了CD11b / Gr1mid募集并降低了肿瘤负担。转基因CD11b-白喉毒素受体小鼠模型中CD11b / Gr1mid子集的耗竭明显降低了肿瘤细胞的增殖。没有证据表明适应性免疫应答参与了CD11b / Gr1mid细胞的促转移作用。另外，在一些大肠癌患者的肝转移中发现了类似的髓样亚群。结论：总的来说，我们的发现突出了髓样细胞（在这种情况下为选择性CD11b / Gr1mid亚型）在维持结直肠癌肝转移发展中的重要性，并确定了抗转移治疗的潜在靶标。

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