Inhibition of inflammatory angiogenesis by distant subcutaneous tumor in mice

• Published in: Life sciences (1973) 2004-04, Vol.74 (23), p.2827-2837
• Main Authors: Belo, A.V, Barcelos, L.S, Ferreira, M.A.N.D, Teixeira, M.M, Andrade, S.P
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenesis Inhibitors - metabolism; Animals; Carcinoma, Ehrlich Tumor - metabolism; Carcinoma, Ehrlich Tumor - pathology; Chemokines; Chemokines - metabolism; Chemotaxis, Leukocyte - physiology; Cytokines; Granulation Tissue - blood supply; Granulation Tissue - metabolism; Granulation Tissue - pathology; Leukocytes, Mononuclear - enzymology; Leukocytes, Mononuclear - pathology; Male; Mice; Neovascularization, Pathologic; Prostheses and Implants; Sponge implants; Surgical Sponges; Tumor; Vascular Endothelial Growth Factor A - metabolism; Wound healing
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2003.09.072

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 × 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-α), 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-α 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.