Quantitative Study of Cancer Stem Cells Growth, Migration and Communication with Cancer Cells in a Microfluidic-based Biomimetic Microenvironment

The discovery of cancer stem cells has changed views of carcinogenesis and providednovel targets for cancer therapy. Cancer stem cells have the ability to initiate tumorformation by undergoing self-renewal and differentiation that result in drug resistance,tumor recurrence and metastasis. However, it is not yet fully understood how tumormicroenvironments regulate the fate of cancer stem cells and how interactions betweencancer stem cells and their niche govern metastatic colonization and enhancetumorigenicity under inflammatory or transforming signals. Quantitative analysis of thebehaviors of cancer stem cells in vitro is limited by the conventional co-culturingmethods which cannot mimic the microenvironment inside the tumor. In order tomonitor and accurately quantify cell-cell interactions in real-time, we propose todevelop a microfluidic-based system which will enable the co-culturing of cancer stemcells and cancer cells in vitro while maintaining a microenvironment similar to the invivo tumor mass. Through the microfluidic networks, we will provide a platform fordisplay of spatial and temporal dynamics of cell-cell communications, and forquantitative measurement of the cellular parameters such as migration distance andareas, and intercellular contacts, for individual and population of cells. By controlling thedimensions of the microchannels and co-culture units, different quantities and ratios ofcancer stem cells and cancer cells will be adjusted to mimic different stages of tumorgrowth, including initiation, progression, regression, and recurrence after chemotherapy.The behavior of lung cancer stem cells and the differentiated lung cancer cells derivedfrom the same lineage will be analyzed, collectively and individually at single cell level,to quantify the cell proliferation, migration, self-renewal, specific differentiation, andcell-cell interactions in the fluctuating microenvironment. The reconstruction of tumormicroenvironment in the microfluidic chip can be further exploited to study thebiological processes involving cancer stems cells and other cells in tumor, which will beimportant for the development of novel and therapeutic strategies against cancer.