In a new study, researchers at the University of Fribourg and University Hospital Zürich have demonstrated calretinin’s possible role in mesothelial cells’ mobility and proliferation as well as in the development of mesothelioma. The research paper, entitled “Overexpression or absence of calretinin in mouse primary mesothelial cells inversely affects proliferation and cell migration,” was published in Respiratory Research.
Mesothelioma is a form of rare but deadly cancer whose incidence has grown in the last decades, mainly due to past exposure to asbestos, one of its main risk factors. This type of cancer affects the mesothelial cells, which form a thin layer that covers, protects, and lubricates serous cavities, consisting of the membranes pleura (lungs), pericardium (heart), and peritoneum (abdomen), as well as the surfaces of internal organs. Diagnosis of mesothelioma usually occurs in an advanced stage of the disease. Calretinin (CR), a Ca 2+ (calcium)-binding protein is found to be absent in normal mesothelial cells. However, in reactive mesothelial cells and in malignant mesothelioma (MM), CR expression is up-regulated. Consequently, CR is one of the few positive biomarkers for MM and is essential for the development and maintenance of human malignant mesothelioma cell lines in vitro.
In light of such evidence and because the molecular pathways and exact role of CR are still largely unknown, the researchers further investigated this protein’s function in the development and function of normal mesothelial cells and thus in the processes that lead to mesothelioma formation. The scientists observed and performed a series of assays, such as histology staining and viability assays, of primary mesothelial cells from wild-type (WT) and CR-deficient (CR−/−) mice. Furthermore, the researchers overexpressed CR in both cell genotypes.
Comparison of morphology, marker proteins, proliferation, cell cycle parameters and mobility profiles shows that both mice exhibited a normal mesothelium, with both cell genotypes showing a normal morphology and expression of mesothelial markers, including the protein mesothelin. In the CR−/− cells, the researchers observed a significantly deceased proliferation and also decreased mesothelial cell layer regeneration. CR up-regulation led to increased cell mobility and proliferation in both genotypes in vitro. The researchers remarked on the findings in their conclusions, stating: “Our results in primary mesothelial cells are in support of CR playing an important role in cell proliferation and mobility. The importance of CR in mesothelioma as a diagnostic marker, as well as its essential function in mesothelioma cell lines emphasize the need of understanding the function and involvement of CR in mesothelium development and mesothelium tissue repair, e.g. after exposure to asbestos.”
Such results corroborate the importance of CR in the signaling pathways in mesothelial cell development and further research is important to more deeply evaluate this protein role in mesothelioma formation in vivo which, if verified, could lead to a potential new therapy strategy.