PORTUGAL - The group of João Sanches from the Instituto Superior Técnico at the University of Lisbon, in collaboration with the group of Raquel Seruca from I3S/IPATIMUP in Porto, has developed a new, simple and effective assay to study the impact of cancer-related molecules in intercellular organization.
Intercellular adhesion is crucial to maintaining normal tissue architecture and E-cadherin is vital to assure that neighboring cells cluster to each other, establishing a correct epithelium. When E-cadherin does not function properly, cells become loose and the tissue becomes disorganized, which is a typical property of cancer.
This knowledge allowed the researchers to develop a new bioimaging strategy, based on the study of cell meshes organization, in order to infer the pathogenic value of E-cadherin mutations associated with cancer.
The process uses microscopic images from cells, where nuclei are used as central points to design a mesh of triangles representing the structure of adjacent cells. Upon this step, quantitative metrics exploring the area and the angles of this “artificial network of triangles” could be extracted to verify the impact of E-cadherin mutations on cellular organization.
The authors of this work verified that this swift, elegant and user-friendly method is able to distinguish cancer-causing E-cadherin mutations, associated with very aggressive invasive tumors, from those protein variants that do not cause any increase in cancer risk.
The results of this collaborative research yielded a methodology which is extremely accurate to study cell-cell interactions, and it represents a new opportunity to study a wide range of proteins that may impact tissue arrangement. Further, it can be used as a new platform to test new drugs that may promote a tighter adhesion between cells and may, thus, stop cancer cell invasion and metastization.
This work was supported by the United States nonprofit organization “No Stomach For Cancer” under the project "Today´s present, tomorrow´s future on the study of germline E-cadherin missense mutations".
Citation: Mestre T, Figueiredo J, Ribeiro AS, Paredes J, Seruca R, Sanches JM. Quantification of topological features in cell meshes to explore E-cadherin dysfunction. Sci Rep. 2016May 6;6:25101. doi: 10.1038/srep25101.