title: Tumor growth, angiogenesis and inflammation in mice lacking receptors for platelet activating factor (PAF).
abstract: 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).
authors.affiliation: Department of Physiology , General Pathology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antonio Carlos 6627, Cx Post 468, Campus Pampulha, CEP 31270-901, Belo Horizonte/MG, Brazil.
authors.forename: M A N D
authors.initials: MA
authors.lastname: Ferreira
authors.forename: L S
authors.initials: LS
authors.lastname: Barcelos
authors.forename: M M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Y S
authors.initials: YS
authors.lastname: Bakhle
authors.forename: S P
authors.initials: SP
authors.lastname: Andrade
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001201:Ascites / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology*; D010529:Peritoneal Cavity; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D012039:Regional Blood Flow / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D019743:Chemokines, CXC; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C039351:platelet activating factor receptor; D009195:Peroxidase; D000118:Acetylglucosaminidase