title: Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis.
abstract: Pro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Hackler
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Reuss
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. ; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Konger
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. ; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA. ; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Travers
authors.affiliation: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. ; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Ravi P
authors.initials: RP
authors.lastname: Sahu
keywords: lung cancer growth and metastasis; platelet-activating factor-receptor; pro-oxidative stressors; systemic immunosuppression