Insights on neoplastic stem cells from gel-based proteomics of childhood germ cell tumors

Haskins, W. E.; Eedala, S.; Avinash Jadhav, Y. L.; Labhan, M. S.; Pericherla, V. C.; Perlman, E. J.

Pediatr Blood Cancer. 2011 Jul 28; 58(5):722-728


BACKGROUND: Childhood germ cell tumors (cGCTs), believed to arise from transformed primordial germ cells by an unknown mechanism, provide a unique model system for investigating cell signaling, pluripotency, and the microenvironment of neoplastic stem cells (NSCs) in vivo. This is the first report of proteomics of cGCTs. PROCEDURE: Four dysgerminomas (DYSs) and four childhood endodermal sinus tumors (cESTs), resembling self-renewing and differentiating NSCs, respectively, were selected. Proteomic studies were performed by 2-DE, SDS-PAGE, and cLC/MS/MS with protein database searching. RESULTS: 2-DE: 9 of 941 spots were differentially regulated with greater than a twofold change in spot volume for at least three of four gels in each group. Two of nine spots had P values for the t-test analysis of comparisons less than 0.001, while the remaining spots had P values from 0.013 to 0.191. Top-ranked proteins were identified in nine of nine spots with 4.0-38% sequence coverage. APOA1, CRK, and PDIA3 were up-regulated in cESTs. TFG, TYMP, VCP, RBBP, FKBP4, and BiP were up-regulated in DYSs. SDS-PAGE: Up-regulation of NF45 and FKBP4 was observed in four of four cESTs and DYSs, respectively. The fold-changes observed correspond with characteristic genetic changes. CONCLUSION: Differential regulation of FKBP4 and NF45, combined with previous research on immunosuppressant binding, suggests that glucocorticoid receptor signaling merits further investigation in cGCTs and NSCs. Pediatr Blood Cancer 2012; 58: 722-728. (c) 2011 Wiley Periodicals, Inc.

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