Dissecting cell type-specific metabolism in pancreatic ductal adenocarcinoma

@article{Lau2020DissectingCT,
  title={Dissecting cell type-specific metabolism in pancreatic ductal adenocarcinoma},
  author={Allison N. Lau and Zhaoqi Li and Laura V Danai and Anna M. Westermark and Alicia M. Darnell and Raphael Ferreira and Vasilena Gocheva and Sharanya Sivanand and Evan C. Lien and Kiera M Sapp and Jared R Mayers and Giulia Biffi and Christopher R Chin and Shawn Michael Davidson and David A. Tuveson and Tyler Jacks and Nicholas J. Matheson and Omer H Yilmaz and Matthew G. Vander Heiden},
  journal={bioRxiv},
  year={2020}
}
Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between various cell types within a mixed population can be limited by 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… Expand
Cell-type specific requirement for pyruvate dehydrogenase in hematopoiesis and leukemia development
TLDR
The requirement of glucose oxidation for leukemia development is inherited from the normal cell of origin and occurs independently of the driver genetic lesion. Expand
Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance
TLDR
A review of how heterotypical reciprocal tumor-stromal and tumor-immune cell interactions in the pancreatic tumor microenvironment can both promote and restrain PDAC development and progression and the role of extracellular matrix (ECM) in potentiating tumor cell proliferation, survival, metastasis, and treatment resistance is discussed. Expand
Physiological impact of in vivo stable isotope tracing on cancer metabolism
TLDR
In depth in vivo profiling of tumor metabolic routes within the appropriate patho-physiological environment will be key to identifying relevant alterations that contribute to cancer onset and progression. Expand
Overexpression of Pyruvate Carboxylase Is Correlated With Colorectal Cancer Progression and Supports Growth of Invasive Colon Cancer HT-29 Cell Line
TLDR
The results showed for the first time that high PC expression levels were significantly correlated with late stage of the cancer, perineural invasion and lymph node metastasis and the overexpression of PC was also significantly associated with poor overall and disease-free survival times of CRC patients. Expand
Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy
TLDR
The dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed and possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota are discussed. Expand
Single-cell metabolomics reveals the metabolic heterogeneity among microbial cells
  • Xuanlin Meng, Fei Tao, Ping Xu
  • Biology
  • 2021
TLDR
A method based on discontinuous mass spectrometry imaging, RespectM, which can detect more than 700 metabolites at a rate of 500 cells per hour, and integrates matrix sublimation, QC-based peak filtering, and batch correction strategies to improve accuracy, which provides RespectM with enough confidence to perform microbial single cell metabolomics analysis. Expand
A pancreas tumor derived organoid study: from drug screen to precision medicine
  • Jia Yao, Man Yang, +4 authors Xun Li
  • Medicine
  • Cancer cell international
  • 2021
TLDR
This review focuses on pancreatic tumor organoids (PTOs), which can mimic the characteristics of the original tumor in vitro, and represents a new strategy for targeted therapy in pancreatic cancer and contribute to the advancement of the field of personalized medicine. Expand
Transporters at the Interface between Cytosolic and Mitochondrial Amino Acid Metabolism
TLDR
How improved methods to study mitochondrial metabolism, define organelle metabolite composition, and visualize cellular gradients allow for a more comprehensive understanding of how transporters facilitate compartmentalized metabolism is examined. Expand
The CAT-SIR is out of the bag: tumors prefer host rather than dietary nutrients
TLDR
This issue of BMC Biology reports an approach where food sources with different isotope labeled carbon ratios can be used, and finds that tumors arising in Drosophila melanogaster procure most of their nutrients from the host. Expand

References

SHOWING 1-10 OF 132 REFERENCES
Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors
TLDR
It is suggested that pancreatic cancer cells consume extracellular protein, including albumin, and that this consumption serves as an important source of amino acids for pancreaticcancer cells in vivo. Expand
Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer.
TLDR
The data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo and argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells. Expand
Metabolic landscape of the tumor microenvironment at single cell resolution
TLDR
A computational pipeline to study metabolic programs in single cells is developed and an overall discordance between analyses of single cells and those of bulk tumors with higher metabolic activity in malignant cells than previously appreciated is reported. Expand
Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo.
TLDR
GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo, and many of these same activities were conserved in cells cultured ex vivo from the tumors. Expand
Metabolic Heterogeneity in Human Lung Tumors
TLDR
These findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature. Expand
Targeting Stromal Glutamine Synthetase in Tumors Disrupts Tumor Microenvironment-Regulated Cancer Cell Growth.
TLDR
This work identifies a previously unrecognized mechanism whereby metabolism of reactive stromal cells is reprogrammed through an upregulated glutamine anabolic pathway and presents a synthetic lethal approach to target tumor stroma and cancer cells simultaneously for desirable therapeutic outcomes. Expand
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion
TLDR
The results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source and highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment. Expand
Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation.
TLDR
PC knockdown induced multinucleation, decreased cell proliferation and colony formation in human NSCLC cells, and reduced tumor growth in a mouse xenograft model are indicated. Expand
Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers
TLDR
Loss of Bcat1 and Bcat2, the enzymes responsible for BCAA use, impairs NSCLC tumor formation, but these enzymes are not required for PDAC tumorformation, arguing that tissue of origin is an important determinant of how cancers satisfy their metabolic requirements. Expand
Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies
TLDR
Experimental evidence that microenvironmental factors regulate tumor metabolism is focused on, and the implications for choosing appropriate model systems and experimental approaches are highlighted. Expand
...
1
2
3
4
5
...