Mechanical compression drives cancer cells toward invasive phenotype
Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subs...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/72496 |
| _version_ | 1826196075421106176 |
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| author | Tse, Janet M. Cheng, Gang Tyrrell, James A. Wilcox-Adelman, Sarah A. Boucher, Yves Jain, Rakesh K. Munn, Lance L. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Tse, Janet M. Cheng, Gang Tyrrell, James A. Wilcox-Adelman, Sarah A. Boucher, Yves Jain, Rakesh K. Munn, Lance L. |
| author_sort | Tse, Janet M. |
| collection | MIT |
| description | Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of “leader cells” that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell–matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion. |
| first_indexed | 2024-09-23T10:20:27Z |
| format | Article |
| id | mit-1721.1/72496 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:20:27Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/724962022-09-26T17:18:49Z Mechanical compression drives cancer cells toward invasive phenotype Tse, Janet M. Cheng, Gang Tyrrell, James A. Wilcox-Adelman, Sarah A. Boucher, Yves Jain, Rakesh K. Munn, Lance L. Massachusetts Institute of Technology. Department of Chemical Engineering Jain, Rakesh Kumar Tse, Janet M. Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of “leader cells” that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell–matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell–substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion. National Institutes of Health (U.S.) (Grant number P01CA080124) National Institutes of Health (U.S.) (Grant number HL64240) 2012-09-04T14:56:10Z 2012-09-04T14:56:10Z 2012-01 2011-08 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/72496 Tse, J. M. et al. “From the Cover: Mechanical Compression Drives Cancer Cells Toward Invasive Phenotype.” Proceedings of the National Academy of Sciences 109.3 (2012): 911–916. Copyright ©2012 by the National Academy of Sciences en_US http://dx.doi.org/10.1073/pnas.1118910109 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Tse, Janet M. Cheng, Gang Tyrrell, James A. Wilcox-Adelman, Sarah A. Boucher, Yves Jain, Rakesh K. Munn, Lance L. Mechanical compression drives cancer cells toward invasive phenotype |
| title | Mechanical compression drives cancer cells toward invasive phenotype |
| title_full | Mechanical compression drives cancer cells toward invasive phenotype |
| title_fullStr | Mechanical compression drives cancer cells toward invasive phenotype |
| title_full_unstemmed | Mechanical compression drives cancer cells toward invasive phenotype |
| title_short | Mechanical compression drives cancer cells toward invasive phenotype |
| title_sort | mechanical compression drives cancer cells toward invasive phenotype |
| url | http://hdl.handle.net/1721.1/72496 |
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