Breast cancer metastasis on chip

Most breast cancer related deaths are not caused directly by the primary tumor, but by secondary tumors formed through metastasis to other organs. Current in-vitro models rarely mimic the initial phase of metastasis: invasion and intravasation, which are strongly modulated by the tumor microenvironment. Hence, we focus on modeling a relevant microenvironment on a chip, namely (1) Extracellular Matrix (ECM) heterogeneity and (2) microvasculature. For (1), we use a flow-focusing device to encapsulate cancer cells in Matrigel beads that mimic the basement membrane. Next, Matrigel beads are cultured in collagen I hydrogel, mimicking the stromal ECM. This way we recapitulate the pre-invasive condition where cancer cells initially reside in a soft basement membrane before invading the fibrous and stiffer stromal ECM. Moreover, modeling vascular network (2) is required to mimic cancer intravasation. We use our 3D sugar-printing technology to create perfusion lumens embedded in matrix, in which endothelial cells can be seeded to recapitulate blood vessels in vitro. Combined with a neighboring channel for cancer cell culture, it is possible to study cancer-vasculature interaction on a single chip. In conclusion, our model of cancer metastasis potentially leads to better understanding of pre-invasive and invasive breast cancer. Furthermore, it has also the capability to add more components of the in vivo cancer microenvironment, such as immune cells or an oxygen gradient.