Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF)

Tumor growth is associated with angiogenesis and inflammation and the endogenous lipid, platelet activating factor (PAF), is a pro-inflammatory and pro-angiogenic mediator. We therefore measured tumor growth, angiogenesis and inflammation in normal (WT) mice and those lacking the receptor for PAF, t...

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Bibliographic Details
Published in:Life sciences (1973) 2007-06, Vol.81 (3), p.210-217
Main Authors: Ferreira, M.A.N.D., Barcelos, L.S., Teixeira, M.M., Bakhle, Y.S., Andrade, S.P.
Format: Article
Language:English
Subjects:
Acetylglucosaminidase - metabolism
Angiogenesis
Animals
Ascites - metabolism
Carcinoma, Ehrlich Tumor - pathology
Chemokine CCL2 - biosynthesis
Chemokines
Chemokines, CXC - biosynthesis
Cytokines
Inflammation - genetics
Inflammation - pathology
Mice
Mice, Inbred BALB C
Mice, Knockout
Neoplasm Transplantation
Neoplasms - blood supply
Neoplasms - genetics
Neoplasms - pathology
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - pathology
PAFR-KO mice
Peritoneal Cavity
Peroxidase - metabolism
Platelet Activating Factor - pharmacology
Platelet Activating Factor - physiology
Platelet Membrane Glycoproteins - genetics
Platelet Membrane Glycoproteins - physiology
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - physiology
Regional Blood Flow - genetics
Regional Blood Flow - physiology
Tumor
Tumor Necrosis Factor-alpha - metabolism
Vascular Endothelial Growth Factor A - metabolism
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Summary:Tumor growth is associated with angiogenesis and inflammation and the endogenous lipid, platelet activating factor (PAF), is a pro-inflammatory and pro-angiogenic mediator. We therefore measured tumor growth, angiogenesis and inflammation in normal (WT) mice and those lacking the receptor for PAF, through gene deletion (PAFR-KO). Growth of solid tumors derived from colon 26 cells was not altered but that from Ehrlich cells was markedly (5-fold) increased in the PAFR-KO mice, relative to the WT strain. Angiogenesis, as tumor content of VEGF or hemoglobin, was increased in both tumors from the mutant strain. Inflammation, as neutrophil and macrophage accumulation and chemokine (CXCL2 and CCL2) content of tumors, was decreased or unchanged in the tumors implying an overall decrease in the inflammatory response in the PAFR-KO strain. We also assessed growth of the Ehrlich tumor in its ascites form, after i.p. injection. Here growth (ascites volume) was inhibited by about 30%, but neutrophil and macrophage numbers were increased in the ascites fluid from the PAFR-KO mice. Angiogenesis in the peritoneal wall, which is not invaded by the tumor cells, was increased but leukocyte infiltration decreased in the mutant strain. Our results show, unexpectedly, that tumor-induced angiogenesis was increased in mice lacking response to PAF, from which we infer that in normal (WT) mice, PAF is anti-angiogenic. Further, although growth was still associated with angiogenesis in PAFR-KO mice, growth was not correlated with inflammation (leukocyte accumulation).
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2007.05.003