Abstract 4870: Proteomics of phyllodes tumor revealed that decorin increase in the extracellular matrix by periostin deficiency decreased cancer cell motility and invasion

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The ability of cancer cells to metastasize is dependent on the interactions of their cell surface molecules with microenvironment. However the tumor microenvironment, especially cancer-associated stroma, is poorly understood. To search for proteins which are present in the stroma, we investigated the phyllodes tumor, which contains breast stromal tissue, specific expression proteins compared with normal tissue by using iTRAQ-based quantitative proteomic approach. Periostin and versican core protein were up-regulated in phyllodes tumor. Decorin, mimecan, hemoglobin subunit alpha, hemoglobin subunit beta and ketatin, type1 cytoskeletal 19 were up-regulated in normal tissue. Periostin and decorin are one of component of the extracellular matrix. Periostin upregulation has been reported in many cancer types and is consequently defined as a tumor-enhancing factor. On the other hand, decorin upregulation inhibits tumor growth by antagonizing tumor angiogenesis. Periostin upregulation in phyllodes tumor and decorin upregulation in normal tissue was validated by immunohistochemical analysis from phyllodes tumor thirty five patients. We determined the interaction between decorin and periostin in phyllodes tumor tissues and breast cancer cell line BT-20 cells, by using immunoprecipitation and mass spectrometry analysis. Furthermore, we uncovered the plasma membrane translocation of decorin from cytoplasm in BT-20 or T-47D cells by siRNA-mediated knockdown of periostin, and detected the secreted decorin to the extracellular medium using Multiple Reaction Monitoring (MRM) method. The periostin siRNA-treated BT-20 cells motility and invasion were prevented by the secreted decorin into the extracellular medium. The overexpression of decorin suppressed the metastatic breast cancer cell line, MDA-MB-231 cells motality and invasion. These results demonstrated the secreted decorin by periostin deficiency decreased cancer cells motality and invasion. This molecular mechanism may become the new target for anti-cancer therapy. Citation Format: Toshiyuki Ishiba, Akira Nakanishi, Takanobu Sato, Tsuyoshi Nakagawa, Makoto Nagahara, Ryo Oono, Hiroyuki Uetake, Kenichi Sugihara, Yoshio Miki. Proteomics of phyllodes tumor revealed that decorin increase in the extracellular matrix by periostin deficiency decreased cancer cell motility and invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4870. doi:10.1158/1538-7445.AM2014-4870