Microscopically small, newly formed tumors may rest in dormant state for months or even years without forming their own blood vessels. It takes a kind of cellular switch to activate genes that are required for the sprouting of new blood vessels. New vessel formation is often accompanied by rapid, invasive tumor growth and metastasis. Drugs directed against key molecules of angiogenesis are already successfully used today to prolong survival of many cancer patients.
Dr. Dr. Amir Abdollahi and Professor Dr. Dr. Peter Huber at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), collaborating with Heidelberg University and US researchers, have investigated what happens at the molecular level when the angiogenetic switch is operated. The investigators studied the genetic response of blood vessel cells (endothelial cells) to known angiogenesis-promoting factors as well as angiogenesis inhibitors. In the “proangiogenetic” state, angiogenesis-promoting genes are switched on, while antiangiogenetic genes are switched off. The organism responds by sprouting new blood vessels. When the gene network is in “antiangiogenetic” state, the reverse is the case, i.e. the formation of blood vessels is prevented.
Measurements of gene activity in tissues samples of patients with diseases of the pancreas have shown the clinical relevance of these findings. From normal pancreatic tissue via chronic pancreatitis through to pancreatic cancer the researchers found a steady increase in the activity of those genes that had been identified in the cell experiment as angiogenesis-promoting. This trend was studied in more detail on a gene called PPARd, whose role in tumor development and angiogenesis had not been known before. The scientists were able to show that the level of PPARd protein steadily increases from normal tissue via pancreatitis tissue through to metastasizing pancreatic cancer. Other tumors, such as breast cancer and prostate cancer, were also found to produce increased levels of the angiogenesis-promoting protein.
In order to study the protein’s actual role in tumor vessel formation, the investigators transplanted skin and lung cancer cells into genetically engineered mice that do not produce their own PPARd. Compared to normal animals, tumor growth in the genetically engineered mice was signifantly slower with poorer supply of vessels.
However, PPARd is only one of many key switches within the angiogenetic network. “Regulation of angiogenesis seems to be more complex than previously assumed,“ says project leader Peter Huber. “Therefore we think that in cancer treatment it is not sufficient to inhibit only one of the participants. Antiangiogenetic therapy might be improved by targeting several of the network’s key switches. One of these could be PPARd.”
The task of the Deutsches Krebsforschungszentrum in Heidelberg (German Cancer Research Center, DKFZ) is to systematically investigate the mechanisms of cancer development and to identify cancer risk factors. The results of this basic research are expected to lead to new approaches in the prevention, diagnosis and treatment of cancer. The Center is financed to 90 percent by the Federal Ministry of Education and Research and to 10 percent by the State of Baden-Wuerttemberg. It is a member of the Helmholtz Association of National Research Centers (Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V.).
Press Officer | alfa
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22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
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