肿瘤细胞循环中的自我播种。
Tumor self-seeding by circulating cancer cells.
机构信息
Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
出版信息
Cell. 2009 Dec 24;139(7):1315-26. doi: 10.1016/j.cell.2009.11.025.
Abstract
Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.
摘要
癌细胞离开原发性肿瘤后可以在远处器官播种转移灶，人们认为这是一个单向的过程。在这里，我们表明循环肿瘤细胞（CTC）也可以定植其起源肿瘤，这个过程我们称之为“肿瘤自播种”。在小鼠中，乳腺癌、结肠癌和黑色素瘤肿瘤的自播种主要由侵袭性 CTC 介导，包括具有骨、肺或脑转移倾向的 CTC。我们发现，肿瘤来源的细胞因子 IL-6 和 IL-8 作为 CTC 的趋化因子，而 MMP1/胶原酶-1 和肌动蛋白细胞骨架成分 fascin-1 是 CTC 浸润到乳腺肿瘤的介质。我们表明，自播种可以通过种子来源的因子加速肿瘤生长、血管生成和基质募集，包括趋化因子 CXCL1。肿瘤自播种可以解释间变、肿瘤大小、血管生成和预后之间的关系，以及在看似完全切除肿瘤后，播散细胞引发的局部复发。
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本文引用的文献
1
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Nature. 2009 Jun 18;459(7249):1005-9. doi: 10.1038/nature08021. Epub 2009 May 6.
2
Metastasis: from dissemination to organ-specific colonization.转移：从播散到器官特异性定植。
Nat Rev Cancer. 2009 Apr;9(4):274-84. doi: 10.1038/nrc2622.
3
Microenvironmental regulation of metastasis.转移的微环境调节
Nat Rev Cancer. 2009 Apr;9(4):239-52. doi: 10.1038/nrc2618. Epub 2008 Mar 12.
4
IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer.白细胞介素-6（IL-6）和信号转导及转录激活因子3（Stat3）是肠道上皮细胞存活和结肠炎相关癌症发生所必需的。
Cancer Cell. 2009 Feb 3;15(2):103-13. doi: 10.1016/j.ccr.2009.01.001.
5
Molecular basis of metastasis.转移的分子基础。
N Engl J Med. 2008 Dec 25;359(26):2814-23. doi: 10.1056/NEJMra0805239.
6
The interleukin-8 pathway in cancer.癌症中的白细胞介素-8信号通路。
Clin Cancer Res. 2008 Nov 1;14(21):6735-41. doi: 10.1158/1078-0432.CCR-07-4843.
7
Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network.由白细胞介素依赖性炎症网络介导的癌基因诱导的衰老
Cell. 2008 Jun 13;133(6):1019-31. doi: 10.1016/j.cell.2008.03.039.
8
Chemokine signaling via the CXCR2 receptor reinforces senescence.通过CXCR2受体的趋化因子信号传导会增强细胞衰老。
Cell. 2008 Jun 13;133(6):1006-18. doi: 10.1016/j.cell.2008.03.038.
9
Systemic endocrine instigation of indolent tumor growth requires osteopontin.惰性肿瘤生长的全身内分泌刺激需要骨桥蛋白。
Cell. 2008 Jun 13;133(6):994-1005. doi: 10.1016/j.cell.2008.04.045.
10
Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer.对单个播散癌细胞进行直接基因分析以预测食管癌的预后和指导治疗选择
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