PF4 Promotes Platelet Production and Lung Cancer Growth
Author(s)
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; ... Show more Show less![Thumbnail](/bitstream/handle/1721.1/107431/PF4%20promotes.pdf.jpg?sequence=4&isAllowed=y)
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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.
Date issued
2017-03-16Department
Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biology; Koch Institute for Integrative Cancer Research at MITJournal
Cell Reports
Citation
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.
Version: Final published version
ISSN
22111247