Malignant cells facilitate lung metastasis by bringing their own soil

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

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Abstract

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.

Original languageEnglish
Pages (from-to)21677-21682
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
Publication statusPublished - 2010 Dec 14

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Cite this

Duda, D. G., Duyverman, A. M. M. J., Kohno, M., Snuderl, M., Steller, E. J. A., Fukumura, D., & Jain, R. K. (2010). Malignant cells facilitate lung metastasis by bringing their own soil. Proceedings of the National Academy of Sciences of the United States of America, 107(50), 21677-21682. https://doi.org/10.1073/pnas.1016234107