Tumours need a steady supply of sufficient nutrients to be able to grow. So they stimulate neighbouring blood vessels to proliferate and sprout using messenger compounds. Scientists from the Max Planck Institute for Neurological Research have now figured out the role of the Vascular Endothelial Growth Factor (VEGF) and its receptor ‘VEGFR-2’ in human lung adenocarcinoma. When VEGF binds to VEGFR-2 on cancer cells, secretion of the growth-factor itself is boosted consequently accelerating tumour growth. In experiments the scientists switched off the growth-factor and proteins responsible for this signalling thereby slowing down tumour growth. The tumours were even reduced in size by employing other inhibitors in combination. Furthermore they also learnt from examinations of lung cancer patients that therapy with these inhibitors only makes sense if the cancer cells express large numbers of VEGFR2. These results can contribute to developing new cancer therapies.
Picture: The feedback loop of the tumour: The cancer cells secrete the growth-factor VEGF (yellow) in order to stimulate nearby blood vessels to introduce small sprouts into the tumour. At the same time, the cells also express VEGFR-2 on their surface, which the VEGF binds to. In this way, the cancer cells are stimulated to produce even more VEGF. © MPI for Neurological Research
Professor Hans Schöler, Director of the Max Planck Institute (MPI) for Molecular Biomedicine in Münster, welcomes the clear commitment to CARE made by the state government of North-Rhine Westphalia: “We are delighted to report that a firm agreement has been reached on the development of this important institute.” The proposed translational research centre will jointly further develop insights from basic research together with the business community so that they can provide a real benefit for patients in the form of new treatment and diagnostic processes. CARE was initiated by the MPI in Münster and Max Planck Innovation, the Max Planck Society’s technology transfer organisation.
Picture: Neural stem cells can become pluripotent. They can then be differentiated into smooth muscular cells that are found, for example, in blood and lymph vessels (red: muscle cells, bleu: cell nuclei). © MPI for Molecular Biomedicine – Kinarm Ko
Max Planck researchers discover how drug resistance in tumours may be prevented: Angiogenesis, the growth of new blood vessels, is a complex process during which different signalling proteins interact with each other in a highly coordinated fashion. The growth factor VEGF and the Notch signalling pathway both play important roles in this process. VEGF promotes vessel growth by binding to its receptor, VEGFR2, while the Notch signalling pathway acts like a switch capable of suppressing angiogenesis. Until recently, scientists had assumed that Notch cancels the effects of VEGF through the downregulation of VEGFR2. Now, researchers at the Max Planck Institute for Molecular Biomedicine and the Westphalian Wilhelms-University in Münster, Germany, were able to demonstrate that defective Notch signalling enables strong and deregulated vessel growth even when VEGF or VEGFR2 are inhibited. In this case, a different VEGF family receptor, VEGFR3, is strongly upregulated, promoting angiogenesis. “This finding might help explain drug resistance issues in certain types of cancer therapy and could become the basis for novel treatment strategies,” suggests Ralf Adams, MPI’s Executive Director and Chair of the Department of Tissue Biology and Morphogenesis.
Proteins are the molecular building blocks and machinery of cells and involved in practically all biological processes. To fulfil their tasks, they need to be folded into a complicated three-dimensional structure. Scientists from the Max Planck Institute of Biochemistry (MPIB) in Martinsried near Munich, Germany, have now analysed one of the key players of this folding process: the molecular chaperone DnaK. “The understanding of these mechanisms is of great interest in the light of the many diseases in which folding goes awry, such as Alzheimer’s or Parkinson’s,” says Ulrich Hartl, MPIB director. The work of the researchers has now been published in Cell Reports.
Picture: The chaperone DnaK binds to new proteins and mediates their folding. Proteins it cannot fold, DnaK transports to GroEL, a highly specialised folding machine. © MPI of Biochemistry
Scientits from the Max Planck Institute in Bad Nauheim use silk from the tasar silkworm as a scaffold for heart tissue: Damaged human heart muscle cannot be regenerated. Scar tissue grows in place of the damaged muscle cells. The scientists are seeking to restore complete cardiac function with the help of artificial cardiac tissue. They have succeeded in loading cardiac muscle cells onto a three-dimensional scaffold, created using the silk produced by a tropical silkworm.
Picture: Disks cut from the cocoon of the tasar silkworm grub provide a basic scaffold for heart muscle cells. The disks are around the same size as cent coins. © MPI for Heart and Lung Research
A hardening of the blood vessels, known as arteriosclerosis, is a widespread disease in western societies which can lead to cardiac infarction and stroke. For treatment normally so called stents are implanted. These artificial tubes which are put into the artery help to prevent the blood flow constriction in the vessel. However, after a surgery very often a restenosis emerges which is the reoccurrence of stenosis, the narrowing of a blood vessel, leading to restricted blood flow again. Scientists from the MPI for Heart and Lung Research have now developed a novel treatment for this restenosis based on small non-coding RNAs (miRNAs 143/145). Micro-RNAs are known only for few years. These short RNA fragments are firmly integrated in the genotype and regulate the completion of proteins. They have an essential influence on the development and the stability of proteins in the cell. The patented findings of the MPI researchers show that there is a connection between miRNA 143/145 and the emergence arteriosclerosis. The Development of new stents eluting miRNA 143/145 mimetics is a very promising approach to combat ateriosclerosis and to inhibit restenosis.
Picture: Fluorescence-microscope picture of artery tissue. In contrast to a normal artery (left half) the vascular wall of miR143 / to 145 knockout mice is significantly extended by plaques. Typically the massive immigration of Makrophagen is (red. Smooth muscle cells are coloured green, nucleuses blue. Copyright: Max-Planck Institute for Heart and Lung Research
A stroke leads to the loss of brain functions due to a lack of blood in the brain. Reasons can be ischemia, a lack of blood flow due to e.g. thrombosis, or leakage of blood. The loss of brain function often results in the inability to move the limbs on one side of the body. Also the thinking power or speech can be affected in a negative way. Now researchers from the Max Planck Institute for Neurological Research and the Department of Neurology at the University Hospital of Cologne found out that not only cell death in the actual stroke area plays a role in the inability of stroke patients to fully regain their original motor capacities. Moreover, the regeneration after a stroke requires intact communication channels between the two halves of the brain. The team is currently examining whether they can regenerate the communication between the brain hemispheres through early and regular stimulation treatment. The long-term aim is to improve motor deficits in stroke patients.
Picture: Stroke damage (white circle) can destroy the communication channels within the brain. This depiction of stretches of fibres show that the damage can also affect fibres between the hemispheres (red) which whither in the course of the illness, thus hindering the exchange of information between the hemispheres. © MPI for Neurological Research.
Heart attacks damage the muscles of the heart and can even cause death in severe cases. However, the human body is able to reverse this process after e.g. myocardial infarction and cardiomyopathy and thus can repair heart muscle cells to a certrain extent. Now researchers from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and the Schüchtermann Klinik in Bad Rothenfelde found out what actually stimualtes this process: A protein called oncostatin M plays a central role in the regression of individual heart muscle cells into their precursor cells. In the future the protein could possibly help to efficiently heal damaged heart muscle tissue and so the scientists plan to improve the self-healing powers of the heart with the help of oncostatin M.
Picture: Cellular regression in diseased heart tissue with the help of oncostatin M: the image shows heart muscles under the fluorescence microscope. The myofibrils are stained red, the cell nuclei blue. © MPI for Heart and Lung Research