Abstract 2365: Cancer cell necrosis induces tumor growth by releasing HMGB1

Abstract

Abstract HMGB1 secreted from cancer cells accelerates invasion and metastasis of them. HMGB1 is released from necrotic cells. In the present study, we examined the differential effect on HMGB1 of apoptosis inducer (AI) from necrosis inducer (NI). CT26 mouse colon cancer cells were treated with trichostatin A (TSA) as AI or doxorubicin (DXR) as NI. DXR treatment increased HMGB1 in cultured medium (CM), whereas TSA did not increase. DXR-treated CM accelerated cell growth and invasion, whereas TSA-treated CM did not accelerate. CT26 cells were inoculated in the bilateral dorsal subcutaneous tissues of mice, which were treated with DXR or TSA by intratumoral injection. After treatment, serum HMGB1 concentrations by DXR and TSA treatments were 228 ng/ml and 21 ng/ml, respectively. After DXR treatment, contralateral tumor and the remnant tumor showed more pronounced growth or re-growth than those treated with TSA. By the lung metastasis model by caudal vein inoculation and the liver metastasis model by intrasplenic inoculation of CT26 cells, lung and liver metastasis was more enhanced by DXR treatment than those by TSA treatment. Metastasis enhancement by DXR treatment was abrogated by anti-HMGB1 co-treatment. Re-growth of linoleic acid-induced quiescent cells was found in DXR-treated mice but not in TSA-treated mice. These finding suggest that HMGB1 released from necrotic cancer cells treated with NI might enhance re-growth and metastasis of remnant cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2365.