Abstract 702: Molecular responses to conductive interstitial thermal therapy of murine 4T1 breast carcinoma in surviving tumors, bone marrow and serum.

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: Ablation of solid tumor with a laser probe (CITT therapy) causes coagulative necrosis in central zone of tumor. The exposure to temperature gradient and immune responses to this treatment may affect homeostasis of surviving cells in surrounding area as well as induce systemic changes. The purpose of this study was 1/ to perform quantitative analyses of 29 transcripts of selected genes in tumor remaining after ablation and in bone marrow 2/ to evaluate changes in 16 cytokines in serum 3/ to compare levels of heat shock proteins in surviving tumors and in control tumors. Methods: Real-time RT-PCR and “delta delta” method was used to determine changes in transcripts in remaining tumors after treatment relative to control tumors. Cytokines in serum were tested using multiplex assay consisting of 16 murine cytokines. Expression of Hsp27 and Hsp70 proteins were determined with Western Blot. Results: 72 hours after thermal ablation of 4T1 tumors the following changes were found in tumor, in bone marrow and in serum of treated mice: 1/Out of 29 quantified transcripts, the level of four transcripts (Csf3 Lifr, Serpin1 and Vcam1) decreased significantly in remaining tumor. Majority of quantified transcripts had lower level in ablated than in control tumors. In bone marrow (BM) an opposite trend was observed. Levels of majority of quantified transcripts in BM increased after ablation as compared to control mice. The transcripts of genes: Cxcl12, Sele, Fgf2, Lifr, Mmp9, Timp3 were significantly higher in BM of mice after tumor ablation. 2/ Out of 16 chemokines tested, 4 chemokines (Il-5, Il-6, Ccl2 (MCP-1) and Ccl5 (RANTES) were detected in serum. There was a consistent increase of Il-5 in serum from ablated animals. 3/ Levels of Hsp27 and Hsp70 proteins were higher in remaining tumor as compared with control tumors. Conclusion The decrease of transcripts in remaining tumor of genes involved in adhesion, extracellular matrix degradation and tumor viability may inhibit re-growth of thermally ablated tumors. The increase of transcripts in bone marrow of treated mice indicates alteration of homeostasis of vascular niche and changes in function of mesenchymal stem cells. The increase of Hsp27 may inhibit apoptosis in remaining tumor. Up-regulation of Interleukin 5 suggests that this cytokine may play role in stimulation of anti-tumor immunity, as observed by other researchers. Further study is needed to determine whether the transcript reported here may be used as markers predicting long term effects of thermal ablation of solid tumors. 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 702. doi:1538-7445.AM2012-702