PF4 promotes platelet production and lung cancer growth
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CitationPucci, Ferdinando, Steffen Rickelt, Andita P. Newton, Christopher Garris, Ernesto Nunes, Charles Evavold, Christina Pfirschke, et al. 2016. “PF4 Promotes Platelet Production and Lung Cancer Growth.” Cell Reports 17 (7): 1764–72. https://doi.org/10.1016/j.celrep.2016.10.031.
AbstractCo-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.
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