Direct visualization of emergent metastatic features within an ex vivo model of the tumor microenvironment.

Ischemic conditions such as hypoxia and nutrient starvation, together with interactions with stromal cells, are critical drivers of metastasis. These conditions arise deep within tumor tissues, and thus, observing nascent metastases is exceedingly challenging. We thus developed the 3MIC-an ex vivo model of the tumor microenvironment-to study the emergence of metastatic features in tumor cells in a 3-dimensional (3D) context.

Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult.

Spontaneous single-nucleotide substitutions and microsatellite mutations have distinct distributions of fitness effects.

The fitness effects of new mutations determine key properties of evolutionary processes. Beneficial mutations drive evolution, yet selection is also shaped by the frequency of small-effect deleterious mutations, whose combined effect can burden otherwise adaptive lineages and alter evolutionary trajectories and outcomes in clonally evolving organisms such as viruses, microbes, and tumors. The small effect sizes of these important mutations have made accurate measurements of their rates difficult.

Direct visualization of emergent metastatic features within an model of the tumor microenvironment.

Metabolic conditions such as hypoxia, nutrient starvation, and media acidification, together with interactions with stromal cells are critical drivers of metastasis. Since these conditions arise deep within tumor tissues with poor access to the bloodstream, the observation of nascent metastases is exceedingly challenging. On the other hand, conventional cell culture studies cannot capture the complex nature of metastatic processes.

The MEMIC is an ex vivo system to model the complexity of the tumor microenvironment.

There is an urgent need for accurate, scalable and cost-efficient models of the tumor microenvironment. Here, we detail how to fabricate and use the metabolic microenvironment chamber (MEMIC) - a 3D-printed ex vivo model of intratumoral heterogeneity. A major driver of the cellular and molecular diversity in tumors is accessibility to the blood stream.