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 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. [Display omitted] •PF4 overexpression is associated with altered lung cancer patient survival•PF4 induces megakaryopoiesis in lung tumor-bearing mice•PF4 increases platelet accumulation in tumor-bearing lungs•Platelets and PF4 promote lung adenocarcinogenesis in mice Tumors can act over extended distances to stimulate tumor-promoting immune responses, but the long-range signals involved remain poorly understood. Pucci et al. now suggest that platelet factor 4 (PF4) can stimulate bone marrow megakaryopoiesis and lung cancer progression.