Cellular Prion Protein PrPC and Ecto-5′-Nucleotidase Are Markers of the Cellular Stress Response to Aneuploidy

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-06, Vol.77 (11), p.2914-2926
• Main Authors: Domingues, Patrícia H., Nanduri, Lalitha S.Y., Seget, Katarzyna, Venkateswaran, Sharavan V., Agorku, David, Viganó, Cristina, von Schubert, Conrad, Nigg, Erich A., Swanton, Charles, Sotillo, Rocío, Bosio, Andreas, Storchová, Zuzana, Hardt, Olaf
• Format: Article
• Language: English
• Subjects: Aneuploidy; Animal models; Biomarkers; Cancer; CD73 antigen; Cell surface; Cellular stress response; Flow cytometry; Immunosuppression; Karyotypes; Nucleotidase; Physiology; Prion protein; Proteins; Reactive oxygen species; Rodents; Stress; Surface markers; Tumors
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-16-3052

Aneuploidy is a hallmark of most human tumors, but the molecular physiology of aneuploid cells is not well characterized. In this study, we screened cell surface biomarkers of approximately 300 proteins by multiparameter flow cytometry using multiple aneuploid model systems such as cell lines, patient samples, and mouse models. Several new biomarkers were identified with altered expression in aneuploid cells, including overexpression of the cellular prion protein CD230/PrPC and the immunosuppressive cell surface enzyme ecto-5′-nucleotidase CD73. Functional analyses associated these alterations with increased cellular stress. An increased number of CD73+ cells was observed in confluent cultures in aneuploid cells relative to their diploid counterparts. An elevated expression in CD230/PrPC was observed in serum-deprived cells in association with increased generation of reactive oxygen species. Overall, our work identified biomarkers of aneuploid karyotypes, which suggest insights into the underlying molecular physiology of aneuploid cells. Cancer Res; 77(11); 2914–26. ©2017 AACR.