Abstract 189: Examining how the extracellular environment alters gene expression in breast cancer

Breast cancer represents 25% of all cancers diagnosed in women globally with almost 1.7 million new cases annually. The average survival rate for patients with early stage breast cancer has increased, however the survival rate for those with metastatic breast cancer has not improved. Metastasis is the number one cause of death in breast cancer patients; it remains a scientific enigma, with no available early detection screen or targeted therapies available to patients. Therefore, understanding how and why cancer cells migrate is of significant biological and clinical interest. Accumulating evidence suggests the metastatic potential of breast cancer is influenced by the composition of the extracellular matrix (ECM). The ECM is composed of fibrous proteins and other non-cellular biomolecules and has a well-documented role in influencing tumour structure and behaviour. We are examining genes that code for several categories of proteins involved in regulating the composition of the ECM. These genes code for proteins that are involved in signal transduction from the cell membrane or for proteins that are secreted into the ECM. We are also examining genes that code for fibrous proteins, glycoproteins, transmembrane proteins, growth factors and proteases. To refine our panel, we used STRING [1], an online database, to examine the relationships between the proteins coded by our genes based on the experimental determination of protein co-expression and protein homology. Using qRT-PCR, we are examining the expression of our refined gene set in three different cell lines, (representing the major sub-categories of breast cancer) which have been cultured on collagen, fibronectin, laminin and stimulated by various growth factors. We extended our study to examine the expression pattern in cells that were maintained in 3-Dimensional culture over a period of 10 days in an attempt to mimic more closely the physiological process. We have determined that there is significant differential gene expression of integrins and growth factor binding proteins as we change the composition of the cells culture environment. This work is helping us to refine a signature set by identifying genes whose expression is dysregulated in response to changes in the stromal environment. We are moving now to determining whether dysregulation of the expression of our gene panel correlates with disease progression by examining matched normal and diseased patient tissue. This could provide the opportunity to generate a novel gene signature that may be used as a prognostic tool to predict invasive cancers. It may also provide information on the design of novel treatment therapies for patients with metastatic cancers. 1. Szklarczyk, D., et al., The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res, 2017. 45(D1): p. D362-d368. Citation Format: Joanne Nolan, Maeve Kiely, Colum P. Dunne, Aoife J. Lowery, Patrick A. Kiely. Examining how the extracellular environment alters gene expression in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 189.