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Selective stimulation of mast cells with a TLR2 agonist inhibits tumor growth in vivo
Author(s) -
Oldford Sharon Ann,
Leiva Carlos A.,
Johnston Brent,
Marshall Jean S.
Publication year - 2008
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.22.1_supplement.1076.14
Subject(s) - lewis lung carcinoma , cancer research , tlr2 , angiogenesis , bone marrow , in vivo , immunology , chemistry , biology , cancer , medicine , metastasis , immune system , innate immune system , microbiology and biotechnology
Mast cells are potent effector cells abundant at the growing edge of solid tumors, where they can enhance angiogenesis. Mast cells stimulated with the Toll‐like receptor‐2 (TLR2) activator Pam 3 CSK 4 lipopeptide (LP) secrete angiostatic chemokines. We hypothesized that LP‐stimulated mast cells would have anti‐tumor potential. LP‐activated bone marrow derived mast cellls (BMMC) significantly inhibited the growth of B16.F10 melanoma (n=10, P=0.0195 ) and LLC1 Lewis lung carcinoma (n=9, P=0.0078 ), in Matrigel plugs in vivo . The presence of BMMC alone had no significant effect on tumour growth. Tumors containing LP‐activated BMMC had reduced blood vessel frequency (B16.F10, n=7, P<0.05; LLC1, n=7, P =0.08) and blood volume (LLC1, n=6, P<0.05 ), correlating with tumor weight (r=0.48, P =0.02). In vitro studies demonstrated this anti‐tumor effect was not attributable to BMMC‐mediated tumor cytotoxicity. Dependence on mast cell expressed TLR2 was confirmed by the lack of LLC1 or B16.F10 tumor inhibition in C57Bl/6 mice using LP and BMMC derived from TLR2 knock‐out mice. Protein array analyses identified several candidate mediators that may contribute to the anti‐tumor effect of LP‐activated BMMC. These findings suggest a novel role for mast cells as intermediaries for anti‐cancer immunotherapies Supported by National Cancer Institute of Canada. SAO is supported by the Cancer Research Training Program.