Platelets guide the formation of early metastatic niches
During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments (“niches”) that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively...
| Asıl Yazarlar: | , , |
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| Diğer Yazarlar: | |
| Materyal Türü: | Makale |
| Dil: | en_US |
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National Academy of Sciences (U.S.)
2015
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| Online Erişim: | http://hdl.handle.net/1721.1/93786 https://orcid.org/0000-0001-7603-8396 |
| _version_ | 1826189481710977024 |
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| author | Labelle, Myriam Begum, Shahinoor Hynes, Richard O |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Labelle, Myriam Begum, Shahinoor Hynes, Richard O |
| author_sort | Labelle, Myriam |
| collection | MIT |
| description | During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments (“niches”) that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form “early metastatic niches.” Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis. |
| first_indexed | 2024-09-23T08:15:47Z |
| format | Article |
| id | mit-1721.1/93786 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:15:47Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/937862022-09-23T11:57:00Z Platelets guide the formation of early metastatic niches Labelle, Myriam Begum, Shahinoor Hynes, Richard O Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Labelle, Myriam Begum, Shahinoor Hynes, Richard O. During metastasis, host cells are recruited to disseminated tumor cells to form specialized microenvironments (“niches”) that promote metastatic progression, but the mechanisms guiding the assembly of these niches are largely unknown. Tumor cells may autonomously recruit host cells or, alternatively, host cell-to-host cell interactions may guide the formation of these prometastatic microenvironments. Here, we show that platelet-derived rather than tumor cell-derived signals are required for the rapid recruitment of granulocytes to tumor cells to form “early metastatic niches.” Granulocyte recruitment relies on the secretion of CXCL5 and CXCL7 chemokines by platelets upon contact with tumor cells. Blockade of the CXCL5/7 receptor CXCR2, or transient depletion of either platelets or granulocytes prevents the formation of early metastatic niches and significantly reduces metastatic seeding and progression. Thus, platelets recruit granulocytes and guide the formation of early metastatic niches, which are crucial for metastasis. Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology National Cancer Institute (U.S.) (Support Grant P30-CA14051) National Cancer Institute (U.S.) (Grant U54-CA126515) National Cancer Institute (U.S.) (Grant U54 CA163109) Howard Hughes Medical Institute 2015-02-05T17:05:25Z 2015-02-05T17:05:25Z 2014-07 2014-04 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/93786 Labelle, Myriam, Shahinoor Begum, and Richard O. Hynes. “Platelets Guide the Formation of Early Metastatic Niches.” Proceedings of the National Academy of Sciences 111, no. 30 (July 14, 2014): E3053–E3061. https://orcid.org/0000-0001-7603-8396 en_US http://dx.doi.org/10.1073/pnas.1411082111 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 (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Labelle, Myriam Begum, Shahinoor Hynes, Richard O Platelets guide the formation of early metastatic niches |
| title | Platelets guide the formation of early metastatic niches |
| title_full | Platelets guide the formation of early metastatic niches |
| title_fullStr | Platelets guide the formation of early metastatic niches |
| title_full_unstemmed | Platelets guide the formation of early metastatic niches |
| title_short | Platelets guide the formation of early metastatic niches |
| title_sort | platelets guide the formation of early metastatic niches |
| url | http://hdl.handle.net/1721.1/93786 https://orcid.org/0000-0001-7603-8396 |
| work_keys_str_mv | AT labellemyriam plateletsguidetheformationofearlymetastaticniches AT begumshahinoor plateletsguidetheformationofearlymetastaticniches AT hynesrichardo plateletsguidetheformationofearlymetastaticniches |