USING A NOVEL 3D DOUBLE-LAYERED TUMOR SPHEROID SYSTEM TO ASSESSS THE EFFECTS OF PACLITAXEL ON CARTINOMA CELLS
Ong, Eric Tu
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E-Cadherin has been commonly accepted as a tumor suppressor. The E-Cadherin mediated cell-cell junctions prevent individual carcinoma cells to break apart from primary tumor to disseminate into surrounding tissue. Recently, this conventional wisdom has been challenged by clinical studies on breast cancer patients showing that expression of E-Cadherin is associated with poor prognosis. A recent in vivo study has demonstrated that E-Cadherin expression functionally supports rapid tumor growth that correlates to a poor clinical outcome. However, due to the difficulty to study tumorigenesis in vivo or recapitulate tumorigenicity in vitro, the mechanism by which E-Cadherin precedes tumor growth is largely unknown. In this study, we develop a novel 3D in vitro system in which we successfully assembled matrigel and collagen gel to mimic the structure and juxtaposed organization of the basement membrane and stromal extracellular matrix. Our system supports breast cancer cells to grow, to organize their multicellular structure, to invade through the matrigel layer into the surrounding collagen I matrix and to organize neighboring stromal tissue. Our 3D system allows us to continuously monitor cell proliferation, invasion, collective migration, and tumor growth simultaneously. We utilize the system to observe E-Cadherin expression and paclitaxel response on carcinoma cells. Our current results indicate the presence of E-Cadherin changes multicellular organization and the invasion of cancer cells, leading to faster tumor growth and increasing the half-maximal inhibitory concentration of paclitaxel.