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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Duyverman, Annique M. M. J. Snuderl, Matija Fukumura, Dai Duda, Dan G. Steller, Ernst J. A. Jain, Rakesh K. Kohno, Mitsutomo |
| Description | Author Affiliation: Duda DG ( Edwin L Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 107 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2010-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain Neoplasms Pathology Lung Neoplasms Neoplasm Metastasis Stromal Cells Animals Cell Line, Tumor Cell Survival Disease Progression Fibroblasts Mice Mice, Inbred C57BL Mice, SCID Neoplasm Transplantation Recombinant Fusion Proteins Genetics Metabolism Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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