Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21677-82. doi: 10.1073/pnas.1016234107. Epub 2010 Nov 22.
Metastatic cancer cells (seeds) preferentially grow in the secondary sites with a permissive microenvironment (soil). We show that the metastatic cells can bring their own soil--stromal components including activated fibroblasts--from the primary site to the lungs. By analyzing the efferent blood from tumors, we found that viability of circulating metastatic cancer cells is higher if they are incorporated in heterotypic tumor-stroma cell fragments. Moreover, we show that these cotraveling stromal cells provide an early growth advantage to the accompanying metastatic cancer cells in the lungs. Consistent with this hypothesis, we demonstrate that partial depletion of the carcinoma-associated fibroblasts, which spontaneously spread to the lung tissue along with metastatic cancer cells, significantly decreases the number of metastases and extends survival after primary tumor resection. Finally, we show that the brain metastases from lung carcinoma and other carcinomas in patients contain carcinoma-associated fibroblasts, in contrast to primary brain tumors or normal brain tissue. Demonstration of the direct involvement of primary tumor stroma in metastasis has important conceptual and clinical implications for the colonization step in tumor progression.
转移癌细胞（种子）优先在具有允许微环境（土壤）的次级部位生长。我们表明，转移细胞可以将自身的基质成分（包括激活的成纤维细胞）从原发性部位带到肺部。通过分析肿瘤的输出血液，我们发现如果循环转移癌细胞包含在异质肿瘤基质细胞片段中，其存活率更高。此外，我们表明，这些共同迁移的基质细胞为伴随的转移癌细胞在肺部提供了早期生长优势。与该假说一致，我们证明了部分耗尽癌相关成纤维细胞（它们与转移癌细胞一起自发扩散到肺组织）可显著减少转移的数量并延长原发性肿瘤切除后的存活时间。最后，我们表明，来自肺癌和其他癌症的脑转移瘤患者的脑转移瘤含有癌相关成纤维细胞，而不是原发性脑肿瘤或正常脑组织。原发肿瘤基质直接参与转移的证明对肿瘤进展中的定植步骤具有重要的概念和临床意义。
