Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression
Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression
复制标题
肿瘤诱导的脾成红细胞样 Ter 细胞的产生促进肿瘤进展
DOI：
10.1016/j.cell.2018.02.061
复制
发表时间：
2018-04-19
期刊：
影响因子：
64.5
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Han, Yanmei;Liu, Qiuyan;Cao, Xuetao
识别肿瘤诱导的白细胞亚群及其衍生的循环因子有助于理解癌症是一种全身性疾病。然而，原发性肿瘤诱导的远端器官中的非白细胞群体如何促进全身扩散仍然不清楚。在这里，我们报告了一个群体的肿瘤诱导，成红细胞样细胞（Ter细胞）来源于巨核细胞-红系祖细胞具有独特的Ter-119（+）CD 45（-）CD 71（+）表型。Ter细胞在晚期肿瘤宿主的肿大脾脏中富集，并通过分泌神经营养因子artemin进入血液促进肿瘤进展。转化生长因子β（TGF-β）和Smad 3活化在Ter细胞生成中是重要的。体内阻断Ter细胞衍生的artemin可抑制肝细胞癌（HCC）的生长，artemin缺乏可消除Ter细胞的促肿瘤能力。我们证实了人肝癌患者脾artemin阳性Ter细胞的存在，并表明血清artemin显著升高与预后不良相关。我们认为Ter细胞和分泌的artemin在癌症进展中起重要作用，具有预后和治疗意义。
Identifying tumor-induced leukocyte subsets and their derived circulating factors has been instrumental in understanding cancer as a systemic disease. Nevertheless, howprimary tumor-induced non-leukocyte populations in distal organs contribute to systemic spread remains poorly defined. Here, we report one population of tumor-inducible, erythroblast-like cells (Ter-cells) deriving from megakaryocyte-erythroid progenitor cells with a unique Ter-119(+)CD45(-)CD71(+) phenotype. Ter-cells are enriched in the enlarged spleen of hosts bearing advanced tumors and facilitate tumor progression by secreting neurotrophic factor arteminintothe blood. Transforming growth factor beta (TGF-beta) and Smad3 activation are important in Ter-cell generation. In vivo blockade of Ter-cell-derived artemin inhibits hepatocellular carcinoma (HCC) growth, and artemin deficiency abolishes Ter-cells' tumor-promoting ability. We confirm the presence of splenic artemin-positive Ter-cells in human HCC patients and show that significantly elevated serum artemin correlates with poor prognosis. We propose that Ter-cells and the secreted artemin play important roles in cancer progression with prognostic and therapeutic implications.