The extracellular matrix (ECM) contributes to the generation of normal breast tissue, and variations in the composition of the ECM have been shown to directly influence the formation and organization of acinus-like and duct-like structures. Specific ECM proteins are also important in the progression of several human cancers, and in particular upregulation of the ECM protein periostin has been linked to poor outcomes in breast cancer. Here we investigated the expression of periostin in biopsy specimens collected from breast cancer patients, as well as determined the differential effects of TGFß and hypoxia on the expression of periostin mRNA and protein in human breast cancer cells. Immunohistological analyses of the breast cancer biopsy specimens indicate that breast cancer tissues expressed different levels of periostin regardless of the stage of the disease and that the expression of periostin tended to decrease as breast cancer progressed. Multiple splice variants of periostin mRNA were expressed by breast cancer cells as determined by RT-PCR. Furthermore, treatments with either TGFß or hypoxia led to significantly different expression of periostin mRNA isoforms and of total level of periostin protein (p<0.05) by breast tumor cells. These observations support the role of periostin in breast cancer progression and suggest a role for specific periostin isoforms in response to changes in the microenvironment including tissue hypoxia and TGFß paracrine signaling from mesenchymal and immune cells.
[This works is 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 Coleman, Amanda Lance, Krista Ricci, Adam Secrest, Didier Dréau. Periostin expression is altered by TGF and hypoxia during breast cancer progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1439. doi:10.1158/1538-7445.AM2013-1439