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: | , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
2017
|
| 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_ | 1826201373701570560 |
|---|---|
| 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 |
| work_keys_str_mv | AT pucciferdinando pf4promotesplateletproductionandlungcancergrowth AT newtonanditap pf4promotesplateletproductionandlungcancergrowth AT garrischristopher pf4promotesplateletproductionandlungcancergrowth AT nunesernesto pf4promotesplateletproductionandlungcancergrowth AT evavoldcharles pf4promotesplateletproductionandlungcancergrowth AT pfirschkechristina pf4promotesplateletproductionandlungcancergrowth AT minokenudsonmari pf4promotesplateletproductionandlungcancergrowth AT pittetmikaelj pf4promotesplateletproductionandlungcancergrowth AT engblomcamilla pf4promotesplateletproductionandlungcancergrowth AT rickeltsteffen pf4promotesplateletproductionandlungcancergrowth AT hynesrichardo pf4promotesplateletproductionandlungcancergrowth AT weisslederralph pf4promotesplateletproductionandlungcancergrowth |