Abstract 1557: High mobility group box 1 secretion supports tumor progression of human malignant mesothelioma

Abstract

Abstract Human malignant mesothelioma (MM) is an aggressive and highly lethal cancer, often associated with exposure to asbestos and erionite. Prognosis is poor, due to late-stage diagnosis and resistance to current conventional therapies. We previously showed that high-mobility group box-1 protein (HMGB1), a damage-associated molecular pattern (DAMP) protein, is involved in the early stages of mesothelial cell transformation. Here we show that HMGB1 establishes an autocrine circuit in MM cells influencing tumor cell proliferation and survival. MM cells express HMGB1 at high levels and secrete HMGB1 into the extracellular space. Accordingly, HMGB1 levels in MM patients’ sera are significantly higher than in those of healthy individuals. In addition, motility, survival and anchorage-independent growth of HMGB1-secreting MM cells were inhibited in vitro by a monoclonal antibody (mAb) against HMGB1, by the recombinant HMGB1 competitive antagonist BoxA and by antibodies against the receptor for advanced glycation end products (RAGE). Inhibition of HMGB1 reduced the growth of MM xenografts in SCID mice and extended survival. Our findings indicate that MM cells become “addicted” to HMGB1 and that targeting HMGB1 can be a promising novel therapeutic approach for MM. 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 1557. doi:1538-7445.AM2012-1557