New research from our lab has identified a novel mechanism by which tumor cells interact with immune cells in the tumor microenvironment. Specifically, we have shown that different types of human and murine cancer cells release branched-chain α-ketoacids (BCKAs) into the extracellular space, which can influence macrophage polarization in a manner that depends on monocarboxylate transporter 1 (MCT1).

Using a combined metabolomics/proteomics platform, we found that uptake of BCKAs fueled macrophage tricarboxylic acid (TCA) cycle intermediates and increased polyamine metabolism. Furthermore, the three BCKAs we tested had different effects on various cellular pathways, including inflammatory signal pathways, phagocytosis, apoptosis, and redox balance.

These findings reveal cancer-derived BCKAs as novel determinants for macrophage polarization, which could be selectively exploited to optimize antitumor immune responses. Ultimately, this research may pave the way for the development of targeted therapies that improve outcomes for cancer patients.

Read full paper "Branched-chain ketoacids derived from cancer cells modulate macrophage polarization and metabolic reprogramming"

Read full paper for free on www.cell.com

Press coverage:

1. Die Entwicklung von Krebszellen verhindern on univie.ac.at
2. Die Entwicklung von Krebszellen verhindern on science.apa.at 
3. Forscher verhindern Unterstützung von Tumoren durch Riesenfresszellen on science.apa.at 
4. Fresszellen am Fördern von Krebs hindern on diepresse.com
5. Biochemischer Schalter gegen Krebs on chemiextra.com
6. Die Entwicklung von Krebszellen verhindern on analytik.de 
7. Targeting the cancer microenvironment on bioportfolio.com
8. Targeting the cancer microenvironment on sciencedaily.com
9. Targeting the cancer microenvironment on worldpharmanews.com

In mice exposed to 24-h feeding/fasting cycles, metformin impaired tumor growth, but only when administered during fasting-induced hypoglycemia.

Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3β (GSK3β) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death. Mechanistically, specific activation of the PP2A-GSK3β axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56δ by low glucose, leading to an active PP2A-B56δ complex with high affinity toward GSK3β.

Get access to this paper on cell.com

The Symposium on Building blocks of Life – from Metabolomics and Proteomics to Systems Biology is jointly organized by VIME (The University of Vienna), Medical University of Vienna and the Austrian Academy of Science.

View the Program -> PROGRAM

Register for the Conference -> ONLINE REGISTRATION  

Submit an Abstract -> ABSTRACT SUMBISSION

More Information: aupa.at

VIME collaborates with Dr. Tetyana Milojevic from the Department of Biophysical Chemistry to investigate the molecular mechanisms of microbial adaptation to outer space conditions such as cold and radiation. The project is funded by the FFG and will investigate samples from the TANPOPO mission.

Read more about this project:

dlr.de/me/desktopdefault.aspx/tabid-1752/2384_read-49013/

medienportal.univie.ac.at/uniview/forschung/detailansicht/artikel/microbes-in-outer-space/

VIME collaborates with Maria Zellner, an expert on Alzheimer Disease and Jürgen König on early and rapid Alzheimer diagnostics. Dr. Maria Zellner coordinates LOAD, a Marie Curie Action for Industry-Academia Partnerships and Pathways (IAPP) on the development of a late-onset- Alzheimer’s disease profile for accurate diagnosis and identification of potential therapeutic approaches.

The Vienna Metabolomics Center is part of the expert consortium of the recently established Austrian Microbiome Initiative (AMICI) headed by Christoph Steininger. In the close collaboration of VIME and AMICI potential fields of collaboration will be explored.

In a close collaboration with the coordinator of the research platform Active Aging Karl-Heinz Wagner the Vienna Metabolomics Center will contribute metabolomic profiles of large cohorts of elderly participants.

Roberta Hansman received a four-year Else Richter grant from the Austrian Science Fund (FWF) to analyze dissolved proteins found in seawater. Proteins comprise about 50% of all living organisms, including the millions of microbes present in every liter of seawater, and thus become a major component of the dissolved organic material found in the ocean. This work will identify and quantify proteins dissolved in seawater in combination with analysis of the exo-metabolome in order to gain insight into what organic material in the ocean is composed of and what role microorganisms play in structuring dissolved organic matter composition. The project will be conducted within the Vienna Metabolomics Center. Roberta Hansman is member of the Microbial Oceanography lab headed by Gerhard Herndl.

A successful fertilisation in plants guarantees the production and high crop yield for human food, e.g. seeds and fruits but also bread, beer and beef! Drought periods inhibit this process and thus dramatically reduce crop yields.
In this project, molecular mechanisms are investigated that enable the pollen to adapt to drought stress conditions adjusting its metabolism to continue its growth to the ovule. The project is financed by the FWF (P29626)

Project summary: http://pf.fwf.ac.at/project_pdfs/pdf_abstracts/p29626e.pdf
Website of Gerhard Obermeyer (Molecular Plant Biophysics, and Biochemistry Lab, Univ. Salzburg) : www.uni-salzburg.at/mpbb