Abstract
Abstract Introduction: The extra cellular matrix molecule Tenascin-C (TNC) in its many isoforms is highly expressed during tissue repair and pathological conditions such as cancer and stress. Utilising the selective pressure of neoadjuvant chemotherapy on carcinoma cells we screened for a subgroup of breast cancer patients with elevated TNC expression and a bad therapy response. TNC expression was correlated with biomarkers, histopathological (stage) and clinical data. Breast cancer cell lines were tested on TNC levels and their expression behaviour under competitive conditions. Methods: Paraffin sections from 68 preoperatively treated breast cancer patients were used for automated immunohistochemistry (IHC) with antibodies targeting TNC, AE1/AE3, Ki67, CD3 and p53. In addition F-18 FDG PET-CT was performed to evaluate therapy response. Protein- and gene expression experiments performed onto six breast cancer cell lines (MCF-7, MDA-MB231, MDA-MB453, SK-BR3, SUM-159, T47-D) showed TNC-expression in MDA-MB453 breast cancer cell line. Gene expression of TNC in hedgehog positive cells (MCF-7) was evaluated after co-cultivation with TNC positive cells (MDA-MB453) by qRT-PCR. The qRT-PCR results confirmed the protein expression results on in vitro stained cell-slides after cell-cell interactions and different growth times. Growth and migration behaviour was studied in 3D-matrigels. Results: We demonstrate that TNC expression in breast cancer is immensely reduced after neoadjuvant chemotherapy (43% of patients lost TNC expression) and that expression profiles after treatment correlate with tumor grade, lymph node status and estrogen receptor status, indicating prognostic value, probably for endocrine treatment. Post-therapeutical correlation and co-localisation of the proliferation marker Ki67 in cancer cells and TNC in the surrounding tumor-stroma of patients having a less beneficial response to chemotherapy. The evaluation of expression levels revealed a linear correlation of TNC and Ki67. Submitting cell lines to selective environmental pressure on cell chamber slides, we observed differentiated staining patterns and cellular localization for TNC. After co-cultivation with MDA-MB453, the hedgehog positive cell line MCF-7 expressed highly elevated levels of TNC. Conclusions: These findings concur with the role of TNC in tissue reorganisation, wound healing and it's growth promoting properties in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 429. doi:10.1158/1538-7445.AM2011-429
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