Even now, radiofrequency ablation (RFA) is accepted as a curative therapy for colorectal cancer liver metastasis (CRLMs). Accumulating data have shown that incomplete radiofrequency ablation (ICR) associates with increase of tumor recurrence and more aggressive malignant phenotype. We determined the mechanisms of this progression, including effectively predict biologic behaviors.We established a mouse model highly mimicking the process of RFA treatment. Functional studies were performed in vitro and in vivo. Our xenograft model unveiled ICR increases the risk in CRLMs recurrence. Here we focused on the heat shock (HS)-induced CRC malignance. Sublethal HS in CRC cell lines provoked cell growth, invasion, and tumor initiation in vitro. Consistently, the xenograft mouse model also confirmed the effects of HS in promoting tumor growth. With Western blot analysis, we found that Fra-1, which is a typical down-stream of the transcription factor ERK1/2, was significantly increased by heat shock stimuli compared with the untreated CRC cells. Furthermore, we demonstrated that silence of Fra-1 in HS treated cells could abolish the effects of HS in promoting malignant phenotype. Significantly, proliferation markers (Ki67, c-Myc, CyclinD1, CDK2), stem cell markers (Sox-2, Sox-9, Oct3/4, Lgr5) and invasion related MMP1 were up-regulated in the HS treated cells and in xenograft model. Taken together, this study established a novel mouse model to study the effect of ICR in CRLM. HS induces CRC proliferation and metastasis by targeting Fra-1, which is a potential prognostic marker and a promising therapeutic strategy for CRC recurrence after RFA treatment.

Citation Format: Zhan-Guo Zhang, Wan-Guang Zhang, Yan-Hui Wu, Hui-Fang Liang, Bi-Xiang Zhang, Xiao-Ping Chen. Incomplete RFA-generated heat shock response provokes colorectal cancer liver metastases (CRLMs) recurrence by inducing cancer cell stemness and invasion. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B47.