Metastasis is the most formidable problem in cancer biology. In metastasis, a cell breaks away from the primary tumor and successfully invades the host stroma. To understand how the metastatic niche contributes to the success of a metastasizing cell, realistic in vitro models are needed. Animals can provide valuable models of the metastatic process, but it is difficult to capture the precise beginning of metastasis and to modulate the chemical and physical environment within the metastatic niche. In contrast, 3D cell cultures are easy to manipulate and they capture some of the spatial and molecular complexity of tumors. We are introducing 3D cell cultures into an in vitro microfabricated tissue engineered model to explore what constitutes a permissive stromal environment. Our stromal microenvironment includes co-cultures of multiple cell types in a tunable hydrogel to mimic the colon tumor microenvironment. 3D colon cancer cell cultures are introduced and chemically triggered to cause cells to detach and migrate. We are applying imaging mass spectrometry protocols developed in our laboratory to image the chemical and spatial gradients that are present in the stromal microenvironment following invasion. Additional samples will be processed for molecular profiling by nano-liquid chromatography tandem mass spectrometry to identify and quantify specific molecules present in the stromal niche. This platform represents an ideal testbed to evaluate the molecular and cellular components of a permissive stromal microenvironment.

Exploring the permissive stromal microenvironment

251st National Meeting (2016)

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