Abstract 5397: The SOCS-1 derived peptides inhibit tumor development

Abstract

Abstract Introduction: Melanoma is the most aggressive form of skin cancer and its incidence has increased dramatically over the years. The murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. In our previous work, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with shRNA affected tumor growth, cell cycle regulation with arrest at the S phase with large-sized nuclei, reduced cell motility and decreased melanoma cell invasion through Matrigel. In vivo, silencing of SOCS- 1 inhibited subcutaneous tumor growth and metastatic development in the lungs. Objectives: Since SOCS-1 is expressed in most melanoma cell lines and bears a relation with tumor invasion, thickness and stage of disease, we synthetized five SOCS-1 peptides based hydrophilic regions suggest regulating protein can be a target of cancer therapy. Suppressor of cytokine signalling 1 (SOCS 1) proteins are negative feedback regulators of several pathways involved in immune response, particularly the JAK/STAT (Janus kinase/Signal Transducer and Activator of Transcription. Results: No effect was found directly on B16F10 Nex 2 in vitro. In this work we hypothesized that SOCS-1 mimetic peptides should act on immune cells. Murine splenocytes from challenged animals and peptide treated was stimulated whole B16F10 Nex 2 lysate and supernatant was measure for ELISA to IFN-gama, IL-6, TNF-alfa and IL-10.The peptides increased the production of IFN-gama, IL-6, TNF-alfa and reduced IL-10 cytokine levels. Moreover, macrophages was stimulated and activation assay was performed. In vivo, the peptides are able to reduced significantly melanoma gorwth in metastatic and subcutaneous model.Additionally, mice knockout IFN-γ and CD1d revealed a inhibition of melanoma cell growth and metastasis. In the present study SOCS-1 derived peptides can be a target of cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5397. doi:1538-7445.AM2012-5397