Inhibition of inflammatory angiogenesis by distant subcutaneous tumor in mice.
We investigated angiogenesis, inflammatory cells accumulation and endogenous production of cytokines in sponge implants of tumor-bearing mice. Seven days after inoculation of Ehrlich tumor cells (2.5 x 10(6)), sponge discs were implanted subcutaneously in the dorsa of mice to induce the formation of fibrovascular tissue. The implants of tumor-bearing and non tumor-bearing animals were assessed for neovascularization and leukocyte accumulation, together with levels of relevant cytokines, vascular endothelial growth factor VEGF), tumor necrosis factor alpha (TNF-alpha), CXCL1-3/KC and CCL2/JE. In the implants of tumor-bearing animals angiogenesis (assessed by hemoglobin content and VEGF levels in the implants) and leukocyte accumulation (assessed by myeloperoxidase -MPO- and N- acetylglucosaminidase-NAG-enzyme activities) were all significantly less than those in the implants of non tumor-bearing animals. Although the chemokine CXCL1-3/KC was lower in the implants of tumor-bearing animals, the chemokine CCL2/JE was increased in this group. The production of TNF-alpha in the implants was not modified by the presence of the subcutaneous tumor. The combination of the methodologies used in this study has provided a novel approach to investigate the interaction between two distinct proliferating tissues that share common features (angiogenesis, cell recruitment, inflammation) and has shown that the predominant inhibitory effect of a tumor mass over repair process is associated with altered cytokine production.
Belo
A V
AV
Department of Physiology and Biophysics, Institute of Biological Sciences-Federal University of Minas Gerais, Av. Antônio Carlos 6627-Campus Pampulha Cx Post 468, Belo Horizonte/MG, Brazil.
Barcelos
L S
LS
Ferreira
M A N D
MA
Teixeira
M M
MM
Andrade
S P
SP
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D006097:Granulation Tissue / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic; D019736:Prostheses and Implants; D015503:Surgical Sponges; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D018925:Chemokines; D042461:Vascular Endothelial Growth Factor A