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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Malignant cells facilitate lung metastasis by bringing their own soil
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Malignant cells facilitate lung metastasis by bringing their own soil

机译：恶性细胞通过带入自己的土壤来促进肺转移

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摘要

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.
机译：转移性癌细胞（种子）优先在允许的微环境（土壤）的次生部位生长。我们表明，转移细胞可以将其自身的土壤基质成分（包括活化的成纤维细胞）从主要部位转移到肺部。通过分析从肿瘤中流出的血液，我们发现，如果将循环转移的癌细胞掺入异型肿瘤基质细胞片段中，它们的生存能力会更高。此外，我们显示这些共同旅行的基质细胞为肺部伴随的转移性癌细胞提供了早期生长优势。与此假设相符，我们证明，与癌相关的成纤维细胞的部分耗竭与转移性癌细胞一起自然扩散到肺组织，显着减少了转移的数量并延长了原发肿瘤切除后的生存期。最后，我们证明与原发性脑瘤或正常脑组织相比，患者肺癌和其他癌的脑转移瘤中含有癌相关的成纤维细胞。原发性肿瘤基质直接参与转移的证明对于肿瘤进展中的定植步骤具有重要的概念和临床意义。

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    Dan G. Duda; Annique M. M. J. Duyverman; Mitsutomo Kohno; Matija Snuderl; Ernst J. A. Steller; Dai Fukumura; Rakesh K. Jain;

  • 作者单位

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

    Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology,Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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