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Platelet Activating Factor Receptor in stromal cells promotes B16F10 melanoma cell tumor growth in vivo through an Interleukin 10‐dependent mechanism: Potential role of systemic immunosuppression
Author(s) -
Sahu Ravi P,
Travers Jeffrey B,
Konger Raymond L
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.243.9
Subject(s) - stromal cell , platelet activating factor receptor , cancer research , melanoma , platelet activating factor , immunosuppression , in vivo , cell growth , chemistry , microbiology and biotechnology , receptor , immunology , biology , biochemistry , antagonist
In vivo tumor growth of B16F10 mouse melanoma cells that lack functional platelet activating factor (PAF)‐receptors (PAFR) is suppressed by overexpression of PAF‐acetylhydrolase (PAF‐AH), which metabolizes PAF. We hypothesized that PAF regulates B16F10 tumor growth via PAFR signaling in stromal cells. We therefore generated B16F10 cells expressing PAFR (B16‐PAFR+) by retroviral transduction and injected 5×10 5 vector control and B16‐PAFR+ cells into both C57Bl6 mice (WT) and PAFR knockout (KO) mice followed by treatment with/without the non‐metabolizable PAFR agonist, carbamyl‐PAF (CPAF; 250 ng ip). No difference in tumor growth in all models was noted in the absence of CPAF. However, CPAF induced a significant increase in tumor growth in WT mice (but not in PAFR‐KO mice) regardless of the PAFR status of the B16F10 cells. Interestingly, anti‐interleukin 10 (IL10)antibodies blocked the ability of CPAF to induce increased tumor growth. Given that a PAF/IL10 pathway is important in regulating ultraviolet B (UVB)‐induced immunosuppression, we demonstrate that UVB exposure (5000 J/m 2 ) also results in increased B16F10 tumor growth in WT mice. These studies indicate that PAF‐dependent B16F10 tumor growth is dependent on stromal PAFR, but not melanoma cell PAFR, and that this is due in part to systemic immunosuppression. Supported by AICR 09A062 & NIH R01 HL062996 grants.