Abstract A7: Participation of atopic condition in melanoma B16-BL6 development

Abstract

Abstract Atopy is a condition characterized by the increase of total serum immunoglobulin E (IgE) levels and a tendency to develop allergic reactions. Allergy in general and specifically atopic dermatitis seems to be associated with an increased risk of melanoma development, but those findings are not conclusive. Mast cells play a central role in allergic reactions because they can be activated by IgE-antigen-dependent crosslinking of the Fc Rl receptor. Since mast cells have been found in the periphery of solid tumors and their presence correlates with tumor angiogenesis and growth, it has been proposed that activation of mast cells may facilitate blood vessel formation and tumor development. We evaluated the melanoma growth in atopic states and the role of mast cells in this process. Since hyper-responsiveness is a critical condition in atopic states, we developed a murine model of atopic condition that allowed us to quantify the increase in the inflammatory state in mice. C57BL/6J mice were sensitized with intravenous (i.v) injection of different concentrations of a monoclonal anti-DNP IgE (SPE-7 clone). Twenty-four hours after IgE administration, atopic condition was evaluated by cutaneous passive anaphylaxis (PCA) assays. A specific antigen for the SPE-7 IgE (DNP-HSA) was i.v. injected together with in Evans blue colorant and extravasation of the colorant was quantified by standard methods. C57BL/6J control and atopic mice were inoculated subcutaneously with 0.5×106B16-BL6 melanoma cells in serum-free Tyrode's buffer 24 hours after vehicle or IgE (750 ng i.v.) administration. Tumor weight was assessed during 4 weeks after inoculation of tumor cells in the ear. Results shown that tumor growth was faster in atopic than non-atopic mice. To investigate the role of mast cells in melanoma growth in atopic condition, we evaluated the tumor weight gain in mast cell deficient Kit (Wsh/Wsh) (W-sh) and mast cell reconstituted (W-sh-rec) mice in normal and atopic conditions. Melanoma tumor growth was impaired in non-atopic and atopic W-sh mice and restored in non-atopic W-sh rec. Interestingly, melanoma growth was greater in W-sh rec atopic mice than in all the groups tested. Our results suggest that atopic condition facilitates melanoma tumor growth and that mast cells participate in this effect. This work was supported by CONACyT Grants 83079 and 79162. Scholarship 210067. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A7.