386206 Engineering Patterned Co-Culture of Breast Cancer Cells and Stromal Cells to Study Cell-Cell Communication in Breast Cancer
Breast cancer is the most common cancer diagnosed in women and human epidermal growth factor receptor (HER2) is overexpressed and/or amplified in ~30% of breast cancer cases which is often co-related with poor prognosis. Trastuzumab serves as the first line therapy for these cases, however, de novo or acquired resistance develop by patients is major obstacle for effective treatment of HER2 positive breast tumors which is often lead to the metastasis of disease. Stromal cells have been shown to play important role in therapeutic resistance and metastasis. Mesenchymal stem cells (MSCs) are multipotent stromal cells, shown to enhance the metastatic potential of developing breast tumors. However, the role of MSCs in HER-2 regulation and its impact on trastuzumab resistance is largely unknown and unexplored. In present study, we explored the effect of crosstalk between adipose derived MSCs and HER2 breast cancer cells (BCCs) on breast cancer progression and trastuzumab resistance. We hypothesized that direct cell to cell contact between MSCs and BCCs is critical for regulation of breast tumor biology.
We engineered a “patterned co-culture model” in order to control the interaction of MSCs with BCCs. We used poly(4-styrenesulfonic acid) (SPS) and poly(diallyldimethylammonium chloride (PDAC) polymers for selective adhesion of cells to create the patterned co-culture of BCCs and aMSCs. Unlike other synthetic and natural polymers, one of the greatest advantages of using SPS and PDAC is that they are biologically inactive material for BCCs and MSCs cells, thus, do not alter the gene or protein expression profile of BCCs and MSCs. Therefore, the results obtained using this method provides true interaction of BCCs with MSCs in co-culture system without interference of interaction of cells with matrix. Our data shows that MSCs regulate key pathways controlling tumor progression when co-cultured with BCCs. We observed upregulation of HER2 in BCCs in our co-culture system. Altogether, our data show that physical contact between MSCs and BCCs is critical to modulate the pathways responsible for metastasis and drug resistances in BCCs.