Dissecting cell-type-specific metabolism in pancreatic ductal adenocarcinoma
Artikel i vetenskaplig tidskrift, 2020

Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between cell types within a mixed population can be challenging due to the rapid turnover of metabolites relative to the time needed to isolate cells. To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used to assess differences between cancer cell and fibroblast metabolism in murine pancreatic cancer organoid-fibroblast co-cultures and tumors. Pancreatic cancer cells exhibited increased pyruvate carboxylation relative to fibroblasts, and this flux depended on both pyruvate carboxylase and malic enzyme 1 activity. Consequently, expression of both enzymes in cancer cells was necessary for organoid and tumor growth, demonstrating that dissecting the metabolism of specific cell populations within heterogeneous systems can identify dependencies that may not be evident from studying isolated cells in culture or bulk tissue.

metabolic heterogeneity

organoid culture

PDAC

malic enzyme 1

cancer biology

pyruvate carboxylase

pancreatic cancer

mouse

Författare

Allison N. Lau

Massachusetts Institute of Technology (MIT)

Zhaoqi Li

Massachusetts Institute of Technology (MIT)

Laura V. Danai

University of Massachusetts

Massachusetts Institute of Technology (MIT)

Anna M. Westermark

Massachusetts Institute of Technology (MIT)

Alicia M. Darnell

Massachusetts Institute of Technology (MIT)

Raphael Ferreira

Massachusetts Institute of Technology (MIT)

Chalmers, Biologi och bioteknik, Systembiologi

Vasilena Gocheva

Massachusetts Institute of Technology (MIT)

Sharanya Sivanand

Massachusetts Institute of Technology (MIT)

Evan C. Lien

Massachusetts Institute of Technology (MIT)

Kiera M. Sapp

Massachusetts Institute of Technology (MIT)

Jared R. Mayers

Massachusetts Institute of Technology (MIT)

Giulia Biffi

Cold Spring Harbor Laboratory

University of Cambridge

Lustgarten Foundation Pancreatic Cancer Research Laboratory

Christopher R. Chin

Massachusetts Institute of Technology (MIT)

Shawn M. Davidson

Princeton University

Massachusetts Institute of Technology (MIT)

David A. Tuveson

Cold Spring Harbor Laboratory

Lustgarten Foundation Pancreatic Cancer Research Laboratory

Tyler Jacks

Massachusetts Institute of Technology (MIT)

Nicholas J. Matheson

Massachusetts Institute of Technology (MIT)

University of Cambridge

Omer Yilmaz

Massachusetts General Hospital

Massachusetts Institute of Technology (MIT)

Matthew G. Vander Heiden

Massachusetts Institute of Technology (MIT)

Dana-Farber Cancer Institute

eLife

2050-084X (ISSN)

Vol. 9

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Immunologi inom det medicinska området

DOI

10.7554/eLife.56782

PubMed

32648540

Mer information

Senast uppdaterat

2020-09-14