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August 4, 2020
Look inside a tumor and you will find not just cancer cells, but also immune cells, fibroblasts, and others, each with their own appetite for destruction or growth. The Vander Heiden Lab aims to dissect functional metabolic differences between cell types within such mixed populations. Specifically, they are studying the unique metabolism of pancreatic ductal adenocarcinoma (PDAC) tumor cells. PDAC is one of the most lethal cancers in the world, yet it remains unknown how different tumor cells such as cancer cells and fibroblasts utilize nutrients and how this contributes to tumor progression and metastasis. New therapies aimed at targeting the distinctive biology—in this case the metabolism—of PDAC cells are needed since current treatments offer little survival benefit.
In a study published in eLife, researchers traced isotope-labeled nutrients incorporated into stable macromolecules. Using these metabolites to compare differences between cancer cell and fibroblast metabolism in mouse models and organoid cell cultures, the team identified how PDAC tumor cells rely on certain enzymes (pyruvate carboxylase and malic enzyme 1) to fuel their growth in the presence of non-cancer cells. Their results demonstrate how isotope labeling within 3D, co-cultured, and in vivo models can be used to identify metabolic activity in particular cell types, and offer insight into potential pathways for curtailing both primary and metastatic tumor growth in PDAC.
This work was funded in part by the MIT Center for Precision Cancer Medicine and the Emerald Foundation. Proof of concept investigations were conducted with support from the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund.