PF4 Promotes Platelet Production and Lung Cancer Growth

Autor: Steffen Rickelt, Andita Newton, Christina Pfirschke, Ralph Weissleder, Richard O. Hynes, Ernesto Nunes, Charles L. Evavold, Christopher Garris, Mikael J. Pittet, Ferdinando Pucci, Mari Mino-Kenudson, Camilla Engblom
Přispěvatelé: 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
Rok vydání: 2016
Předmět:
Blood Platelets
0301 basic medicine
Lung Neoplasms
Carcinogenesis
Adenocarcinoma of Lung
Bone Marrow Cells
Adenocarcinoma
Biology
Megakaryocytes/metabolism
Platelet Factor 4
Article
General Biochemistry
Genetics and Molecular Biology
Proto-Oncogene Proteins p21(ras)
Mice
03 medical and health sciences
Carcinogenesis/metabolism/pathology
Lung Neoplasms/blood/pathology
medicine
Animals
Humans
Platelet Factor 4/metabolism
Cell Lineage
Platelet
Lung cancer
lcsh:QH301-705.5
Cell Proliferation
Megakaryopoiesis
Tumor microenvironment
Bone Marrow Cells/metabolism
Cancer
medicine.disease
Survival Analysis
3. Good health
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
Immunology
Adenocarcinoma/blood/pathology
Disease Progression
Cancer research
Blood Platelets/metabolism
Bone marrow
Proto-Oncogene Proteins p21(ras)/metabolism
Megakaryocytes
Platelet factor 4
Zdroj: Cell Reports, Vol. 17, No 7 (2016) pp. 1764-1772
Cell Reports, Vol 17, Iss 7, Pp 1764-1772 (2016)
Elsevier
ISSN: 2211-1247
Popis: 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)
Databáze: OpenAIRE
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