Abstract
Abstract Involved in the maintenance of normal breast tissue, the extracellular matrix (ECM) also supports the progression of several human cancers. In particular, both periostin and TGF-β-induced (β-Ig-H3) whose expression is regulated by transforming growth factor-β (TGF-β) signaling, are differentially expressed in many human cancers. While a link between increased periostin expression and poor breast cancer outcomes has been shown, our recent data suggest that overall periostin expression is variable and is poorly correlated with human breast cancer progression. Therefore, in this study we investigated the ratio between periostin and β-Ig-H3 expression and the relationship between TGF-β signaling and expression of these ECM proteins by cancer cells and stromal cells during human breast cancer progression. Expressions of periostin and β-Ig-H3 were determined in biopsy specimens collected from 61 breast cancer patients by immunohistochemistry and correlated with clinico-pathologic features. Additionally, periostin, β-Ig-H3, and TGF-β expression in multiple stroma and tumor cells were evaluated in vitro using western-blots and ELISAs. Increases in the periostin / ß-Ig-H3 ratio correlated with increased the AJCC stage and progesterone positive status of the breast cancer specimens tested (p<0.05). In vitro, murine L929 fibroblasts and 4T1 mammary cancer cells secreted higher periostin concentrations compared to J774 and RAW macrophages (p<0.05). Furthermore, the periostin / ß-Ig-H3 protein expression ratio of 4T1 cells was higher than those of J774 and RAW cells. Following treatment with TGF-ß that activated the SMAD pathway, L929 and 4T1 cells expressed higher periostin concentrations (p<0.05). In contrast, the high ß-Ig-H3 secretion by L929 fibroblasts and J774 macrophages remained unchanged following TGFß treatment (n.s.). These observations support a role for TGF-ß and periostin signaling loops between stroma and cancer cells in the microenvironment and may indicate a role of the periostin / ß-Ig-H3 ratio as a predictor of breast cancer aggressiveness. [This works was supported by grants from the Department of Defense Era of Hope research program (BC044778) and the National Science Foundation EFRI program (CBE0736007)] Citation Format: Michelle M. Coleman, Anindita Das Burman, Amanda L. Lance, Didier Dreau. Mediated by cancer cell and stroma cell TGF-β signaling, the periostin / β-Ig-H3 expression ratio is altered during breast cancer progression. [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 3466. doi:10.1158/1538-7445.AM2014-3466
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
