+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Pheochromocytoma/paraganglioma preclinical models: which to use and why?


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Pheochromocytomas/paragangliomas (PPGLs) are rare neuroendocrine tumours linked to more than 15 susceptibility genes. PPGLs present with very different genotype/phenotype correlations. Certainly, depending on the mutated gene, and the activated intracellular signalling pathways, as well as their metastatic potential, each tumour is immensely different. One of the major challenges in in vitro research, whatever the study field, is to choose the best cellular model for that study. Unfortunately, most of the time there is not ‘a best’ cell model. Thus, in order to avoid observations that could be related to and/or dependent on a specific cell line, researchers often perform the same experiments using different cell lines simultaneously. The situation is even more complicated when there are only very few cell models obtained in different species for a disease. This is the case for PPGLs. In this review, we will describe the characteristics of the different cell lines and of mouse models, trying to understand if there is one that is more appropriate to use, depending on which aspect of the tumours one is trying to investigate.

          Related collections

          Most cited references65

          • Record: found
          • Abstract: found
          • Article: not found

          Extension of life-span by introduction of telomerase into normal human cells.

          Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced straining for beta-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.
            • Record: found
            • Abstract: found
            • Article: not found

            Comprehensive Molecular Characterization of Pheochromocytoma and Paraganglioma.

            We report a comprehensive molecular characterization of pheochromocytomas and paragangliomas (PCCs/PGLs), a rare tumor type. Multi-platform integration revealed that PCCs/PGLs are driven by diverse alterations affecting multiple genes and pathways. Pathogenic germline mutations occurred in eight PCC/PGL susceptibility genes. We identified CSDE1 as a somatically mutated driver gene, complementing four known drivers (HRAS, RET, EPAS1, and NF1). We also discovered fusion genes in PCCs/PGLs, involving MAML3, BRAF, NGFR, and NF1. Integrated analysis classified PCCs/PGLs into four molecularly defined groups: a kinase signaling subtype, a pseudohypoxia subtype, a Wnt-altered subtype, driven by MAML3 and CSDE1, and a cortical admixture subtype. Correlates of metastatic PCCs/PGLs included the MAML3 fusion gene. This integrated molecular characterization provides a comprehensive foundation for developing PCC/PGL precision medicine.
              • Record: found
              • Abstract: found
              • Article: not found

              Pheochromocytoma and paraganglioma pathogenesis: learning from genetic heterogeneity.

              The neuroendocrine tumours pheochromocytomas and paragangliomas carry the highest degree of heritability in human neoplasms, enabling genetic alterations to be traced to clinical phenotypes through their transmission in families. Mutations in more than a dozen distinct susceptibility genes have implicated multiple pathways in these tumours, offering insights into kinase downstream signalling interactions and hypoxia regulation, and uncovering links between metabolism, epigenetic remodelling and cell growth. These advances extend to co-occurring tumours, including renal, thyroid and gastrointestinal malignancies. Hereditary pheochromocytomas and paragangliomas are powerful models for recognizing cancer driver events, which can be harnessed for diagnostic purposes and for guiding the future development of targeted therapies.

                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                December 2020
                24 November 2020
                : 9
                : 12
                : R251-R260
                [1 ]Department of Experimental and Clinical Biomedical Sciences , University of Florence, Florence, Italy
                [2 ]Department of Experimental and Clinical Medicine , University of Florence, Florence, Italy
                Author notes
                Correspondence should be addressed to E Rapizzi: elena.rapizzi@ 123456unifi.it
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                : 16 November 2020
                : 24 November 2020

                pheochromocytoma/paraganglioma,cell models,animal models


                Comment on this article