Abstract
A particle-rich cytoplasmic structure (PaCS) concentrating ubiquitin–proteasome system (UPS) components and barrel-like particles in clear, cytoskeleton- and organelle-free areas has recently been described in some neoplasms and in genetic or infectious diseases at risk of neoplasia. Ultrastructurally similar particulate cytoplasmic structures, interpreted as glycogen deposits, have previously been reported in clear-cell neoplasms and some fetal tissues. It remains to be investigated whether the two structures are the same, colocalize UPS components and polysaccharides, and have a role in highly proliferative cells such as fetal and neoplastic cells. We used immunogold electron microscopy and confocal immunofluorescence microscopy to examine human and mouse fetal tissues and human neoplasms. Fetal and neoplastic cells both showed colocalization of polyubiquitinated proteins, 19S and 20S proteasomes, and polysaccharides, both glycogen and chondroitin sulfate, inside cytoplasmic structures showing all distinctive features of PaCSs. Poorly demarcated and/or hybrid (ribosomes admixed) UPS- and glycogen-enriched areas, likely stages in PaCS development, were also seen in some fetal cells, with special reference to those, like primary alveolar pulmonary cells or pancreatic centroacinar cells, having a crucial role in organogenesis. UPS- and glycogen-rich PaCSs developed extensively in clear-cell neoplasms of the kidney, ovary, pancreas, and other organs, as well as, in infantile, development-related tumors replicating fetal patterns, such as choroid plexus papilloma. UPS-mediated, ATP-dependent proteolysis and its potential energy source, glycogen metabolism, may have a crucial, synergic role in embryo-/organogenesis and carcinogenesis.
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Acknowledgments
We are gratefully indebted to Dr. O. Baba (Biostructural Science, Tokyo Medical and Dental University, Tokyo, Japan) for kindly providing us with the anti-glycogen antibody. This work was supported by grants from the Italian Ministry of Health to Fondazione IRCCS Policlinico San Matteo and University of Pavia (Grant No. RF-2010-2310098), and from Fondazione Cariplo (Grants Nos. 2009-2532, 2011-0485 and 2012-0529).
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Vittorio Necchi, Patrizia Sommi, and Agostina Vitali have contributed equally to this work.
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Necchi, V., Sommi, P., Vitali, A. et al. Polyubiquitinated proteins, proteasome, and glycogen characterize the particle-rich cytoplasmic structure (PaCS) of neoplastic and fetal cells. Histochem Cell Biol 141, 483–497 (2014). https://doi.org/10.1007/s00418-014-1202-5
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DOI: https://doi.org/10.1007/s00418-014-1202-5