(571d) In Vitro Breast Cancer Model to Study Stroma Mediated Signaling in Breast Cancer

The paracrine signaling pathways between breast cancer cells (BCCs) and stromal cells are critical for epithelial-mesenchymal transition (EMT) and metastasis. Several cancer studies have focused mainly on the mutated and highly proliferated cancer cell; however, during the last decade, the role of the tumor microenvironment (TME) has been shown to play a significant role in the malignant evolution of neoplasia and cancer progression. Despite the importance of the tumor microenvironment, the current scientific understanding of the interactions between tumor cells and the surrounding cells remains limited. The use of cell systems or in vitro models that more closely recapitulates the in vivo like signaling in BCCs would be desirable to increase the possibility of translating results of culture models into patient care. It is known that the TME of mammary gland composes of ECM and stromal cells in a well ordered architecture that disrupt during tumor initiation and progression. In the present study we investigated the interactions between breast cancer cells and stromal cells. A patterned co-culture system was developed using microfabrication and micropatterning techniques and the results were compared with monocultures of breast cancer cells. Cellular interactions in patterned co-culture were characterized by evaluating the morphology, expression of human epidermal growth factor receptor-2 (HER-2), and DNA microarray analysis. The results showed that co-culture of BCCs with stromal cells affected the proliferation, gene and protein expression as compared to monoculture, thus, modulates the biology of breast cancer cells. The in vitro patterned co-culture model is capable of controlling cell placement and size of the cells arrays and provides a valuable tool to study paracrine cell-cell interactions