Monday, 01 February, 2021
Basement membrane stiffness determines metastases formation
Extraordinary CeNS member Prof. Hauke Clausen-Schaumann and his co-workers from Erler Group at the Biotech Research & Innovation Centre (BRIC) in Copenhagen have discovered that the rigidity of a thin membrane structure encompassing cells and lining all vessels regulates how easily cancer cells can breach tissues to spread through the body, and is thus a key determinant of cancer patient survival. The results have been published in Nature Materials.
By nanomechanical measurements, Hauke Clausen-Schaumann and his group could for the first time directly demonstrate the effect of Netrin 4 on the mechanical properties of the basal membrane. (Picture: CANTER)
By nanomechanical measurements, Hauke Clausen-Schaumann and his group could for the first time directly demonstrate the effect of netrin-4 on the mechanical properties of the pulmonary basal membrane. (Picture: CANTER) Preventing metastasis formation is one of the key factor in prolonging cancer patient survival. The study shows that in various cancer types, metastasis formation and thus patient survival is determined by the mechanical properties of the basal membrane, which is precisely tuned by the small molecule netrin-4, through competitive binding to the laminin network: High levels of netrin-4 soften the basal membrane and increase survival rates in mouse models and in human patients. How netrin 4 modulates the biomechanics of native and artificial basal membranes was investigated by atomic force microscopy based nanoindentation and pressure myography analysis, combined with theoretical modelling. The effect on metastasis formation was shown in cell culture experiments, animal models, and by analyzing large human patient data sets with bioinformatics tools. The results of this study might lead to new treatment strategies for cancer patients, for example by administering netrin-4 or a suitable mRNA.
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