PF4 Promotes Platelet Production and Lung Cancer Growth

Ferdinando Pucci, Steffen Rickelt, Andita P. Newton, Christopher Garris, Ernesto Nunes, Charles Evavold, Christina Pfirschke, Camilla Engblom, Mari Mino-Kenudson, Richard O. Hynes, Ralph Weissleder, Mikael J. Pittet

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1764-1772
Number of pages9
JournalCell Reports
Volume17
Issue number7
DOIs
StatePublished - Nov 8 2016
Externally publishedYes

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Platelets
Tumor Microenvironment
Tumors
Lung Neoplasms
Blood Platelets
Growth
Neoplasms
Endocrine Gland Neoplasms
Bone Marrow
Platelet Factor 4
Genetic Models
Hematopoiesis
Bone
Communication
Lung
Survival
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Pucci, F., Rickelt, S., Newton, A. P., Garris, C., Nunes, E., Evavold, C., ... Pittet, M. J. (2016). PF4 Promotes Platelet Production and Lung Cancer Growth. Cell Reports, 17(7), 1764-1772. https://doi.org/10.1016/j.celrep.2016.10.031

PF4 Promotes Platelet Production and Lung Cancer Growth. / Pucci, Ferdinando; Rickelt, Steffen; Newton, Andita P.; Garris, Christopher; Nunes, Ernesto; Evavold, Charles; Pfirschke, Christina; Engblom, Camilla; Mino-Kenudson, Mari; Hynes, Richard O.; Weissleder, Ralph; Pittet, Mikael J.

In: Cell Reports, Vol. 17, No. 7, 08.11.2016, p. 1764-1772.

Research output: Contribution to journalArticle

Pucci, F, Rickelt, S, Newton, AP, Garris, C, Nunes, E, Evavold, C, Pfirschke, C, Engblom, C, Mino-Kenudson, M, Hynes, RO, Weissleder, R & Pittet, MJ 2016, 'PF4 Promotes Platelet Production and Lung Cancer Growth', Cell Reports, vol. 17, no. 7, pp. 1764-1772. https://doi.org/10.1016/j.celrep.2016.10.031
Pucci F, Rickelt S, Newton AP, Garris C, Nunes E, Evavold C et al. PF4 Promotes Platelet Production and Lung Cancer Growth. Cell Reports. 2016 Nov 8;17(7):1764-1772. https://doi.org/10.1016/j.celrep.2016.10.031
Pucci, Ferdinando ; Rickelt, Steffen ; Newton, Andita P. ; Garris, Christopher ; Nunes, Ernesto ; Evavold, Charles ; Pfirschke, Christina ; Engblom, Camilla ; Mino-Kenudson, Mari ; Hynes, Richard O. ; Weissleder, Ralph ; Pittet, Mikael J. / PF4 Promotes Platelet Production and Lung Cancer Growth. In: Cell Reports. 2016 ; Vol. 17, No. 7. pp. 1764-1772.
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