Patterned Co-Culture of Breast Cancer Cells and Stromal Cells As An In Vitro Breast Cancer Model

The paracrine signaling pathways between breast cancer cells (BCCs) and stromal cells are critical for epithelial-mesenchymal transition (EMT) and metastasis. The transformation of normal cells to malignant cells and malignant cells to metastatic cells may depend on the interaction between the cells and the cell microenvironment. 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. Considering the rebuilding of TME, in the present study, we engineered a platform to co-culture breast cancer cells (BCCs) with stromal cells. 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 the mammary gland is composed of ECM and stromal cells in a well ordered architecture that is disrupted during tumor initiation and progression. Therefore, we engineered an in vitro patterned co-culture model having structural similarities of in vivo by recreating the cell-cell interaction in the TME. Recent advances in micro-fabrication techniques have made it possible to engineer surfaces that mimic in vivo mechanical and structural aspects of cellular microenvironment. Using the same approach we have established the patterned co-culture of BCCs and stromal cells. 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. Our 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.