PF4 Promotes Platelet Production and Lung Cancer Growth
Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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2017
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| Online Access: | http://hdl.handle.net/1721.1/107431 https://orcid.org/0000-0002-5224-7764 https://orcid.org/0000-0001-7603-8396 https://orcid.org/0000-0003-0828-4143 |
| _version_ | 1811081693459644416 |
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| author | Pucci, Ferdinando Newton, Andita P. Garris, Christopher Nunes, Ernesto Evavold, Charles Pfirschke, Christina Mino-Kenudson, Mari Pittet, Mikael J. Engblom, Camilla Rickelt, Steffen Hynes, Richard O. Weissleder, Ralph |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Pucci, Ferdinando Newton, Andita P. Garris, Christopher Nunes, Ernesto Evavold, Charles Pfirschke, Christina Mino-Kenudson, Mari Pittet, Mikael J. Engblom, Camilla Rickelt, Steffen Hynes, Richard O. Weissleder, Ralph |
| author_sort | Pucci, Ferdinando |
| collection | MIT |
| description | Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis. Additionally, anti-platelet treatment controlled mouse lung cancer progression, further suggesting that platelets can modulate the tumor microenvironment to accelerate tumor outgrowth. These findings support PF4 as a cancer-enhancing endocrine signal that controls discrete aspects of bone marrow hematopoiesis and tumor microenvironment and that should be considered as a molecular target in anticancer therapy. |
| first_indexed | 2024-09-23T11:50:35Z |
| format | Article |
| id | mit-1721.1/107431 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:50:35Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | mit-1721.1/1074312022-09-27T22:20:19Z PF4 Promotes Platelet Production and Lung Cancer Growth Pucci, Ferdinando Newton, Andita P. Garris, Christopher Nunes, Ernesto Evavold, Charles Pfirschke, Christina Mino-Kenudson, Mari Pittet, Mikael J. Engblom, Camilla Rickelt, Steffen Hynes, Richard O. Weissleder, Ralph Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Rickelt, Steffen Hynes, Richard O. Weissleder, Ralph Co-option of host components by solid tumors facilitates cancer progression and can occur in both local tumor microenvironments and remote locations. At present, the signals involved in long-distance communication remain insufficiently understood. Here, we identify platelet factor 4 (PF4, CXCL4) as an endocrine factor whose overexpression in tumors correlates with decreased overall patient survival. Furthermore, engineered PF4 over-production in a Kras-driven lung adenocarcinoma genetic mouse model expanded megakaryopoiesis in bone marrow, augmented platelet accumulation in lungs, and accelerated de novo adenocarcinogenesis. Additionally, anti-platelet treatment controlled mouse lung cancer progression, further suggesting that platelets can modulate the tumor microenvironment to accelerate tumor outgrowth. These findings support PF4 as a cancer-enhancing endocrine signal that controls discrete aspects of bone marrow hematopoiesis and tumor microenvironment and that should be considered as a molecular target in anticancer therapy. Ludwig Center at MIT use Ludwig Center for Molecular Oncology at MIT (Massachusetts/Cancer Research Postdoc fellowship) Howard Hughes Medical Institute National Institute of Mental Health (U.S.) (U54-CA12651) National Institute of Mental Health (U.S.) (U54-CA16310) Deutsche Forschungsgemeinschaft (RI2408/1-1) C.H. Boehringer Sohn (Boehringer Ingelheim Funds to C. Engblom) European Molecular Biology Organization (long-term fellowship (ALTF 1535-2011)) Massachusetts General Hospital. Executive Committee On Research (Funds for Medical Discovery Fellowship) 2017-03-16T14:20:38Z 2017-03-16T14:20:38Z 2017-03-16 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/107431 Pucci, Ferdinando, Steffen Rickelt, Andita P. Newton, Christopher Garris, Ernesto Nunes, Charles Evavold, Christina Pfirschke, et al. “PF4 Promotes Platelet Production and Lung Cancer Growth.” Cell Reports 17, no. 7 (November 2016): 1764–1772. doi:10.1016/j.celrep.2016.10.031. https://orcid.org/0000-0002-5224-7764 https://orcid.org/0000-0001-7603-8396 https://orcid.org/0000-0003-0828-4143 en_US http://dx.doi.org/10.1016/j.celrep.2016.10.031 Cell Reports Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier |
| spellingShingle | Pucci, Ferdinando Newton, Andita P. Garris, Christopher Nunes, Ernesto Evavold, Charles Pfirschke, Christina Mino-Kenudson, Mari Pittet, Mikael J. Engblom, Camilla Rickelt, Steffen Hynes, Richard O. Weissleder, Ralph PF4 Promotes Platelet Production and Lung Cancer Growth |
| title | PF4 Promotes Platelet Production and Lung Cancer Growth |
| title_full | PF4 Promotes Platelet Production and Lung Cancer Growth |
| title_fullStr | PF4 Promotes Platelet Production and Lung Cancer Growth |
| title_full_unstemmed | PF4 Promotes Platelet Production and Lung Cancer Growth |
| title_short | PF4 Promotes Platelet Production and Lung Cancer Growth |
| title_sort | pf4 promotes platelet production and lung cancer growth |
| url | http://hdl.handle.net/1721.1/107431 https://orcid.org/0000-0002-5224-7764 https://orcid.org/0000-0001-7603-8396 https://orcid.org/0000-0003-0828-4143 |
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