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  • Oncogenomics
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Proteomic identification of the wt-p53-regulated tumor cell secretome

Oncogene volume 25, pages 7650–7661 (2006)Cite this article

Abstract

Tumor–stroma interactions play a major role in tumor development, maintenance and progression. Yet little is known on how the genetic alterations that underlie cell transformation elicit cell extrinsic changes modulating heterotypic cell interactions. We hypothesized that these events involve a modification in the complement of secreted proteins by the cell, acting as mediators of intercellular communication. To test this hypothesis, we examined the role of wt-p53, a major tumor suppressor, on the tumor microenvironment through its regulation of secreted factors. Using a combination of 2-DE and cICAT proteomic techniques, we found a total of 111 secreted proteins, 39 of which showed enhanced and 21 inhibited secretion in response to wt-p53 expression. The majority of these were not direct targets of p53 transcription factor activity, suggesting a novel role for wt-p53 in the control of intracellular protein trafficking and/or secreted protein stability. Evidence for p53-controlled post-translational modifications on nine secreted proteins was also found. These findings will enhance our understanding of wt-p53 modulated interactions of the tumor with its environment.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

β-2M:

beta-2-microglobulin

2-DE:

two-dimensional gel electrophoresis

cICAT, cleavable isotope-coded affinity tag technology; CM:

conditioned media

ECM:

extracellular matrix

FGF-4:

fibroblast growth factor-4

Gal-1:

Galectin-1

Gal-3:

galectin-3

Pre-alb:

pre-albumin

SPARC:

secreted protein with acidic and cysteine-rich domains

TGF-β:

transforming growth factor beta

TSP1:

thrombospondin-1

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Acknowledgements

We thank Drs JC Lucchesi, D Pallas, I Matsumura and P Vertino for their support. This work was supported by National Institutes of Health (NIH) grants CA 86335 (to EGVM); NCRR 02878, 12878, 13948 (to Microchemical and Proteomics Facility), the Pediatric Brain Tumor Foundation of the US (to EGVM) and the American Brain Tumor Association (to BP), the Genetics and Molecular Biology (GMB) program of the Graduate Division of Biological and Biomedical Sciences (GDBBS) of Emory University, and the National Science Foundation (NSF) (PRISM; DGE0231900).

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Authors and Affiliations

  1. Department of Neurosurgery, Laboratory of Molecular Neuro-Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    F W Khwaja, B Pyrzynska & E G Van Meir

  2. Department of Hematology/Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    F W Khwaja, B Pyrzynska & E G Van Meir

  3. Emory University Microchemical and Proteomics Facility, Emory University School of Medicine, Atlanta, GA, USA

    P Svoboda, M Reed & J Pohl

Authors
  1. F W Khwaja
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  2. P Svoboda
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  3. M Reed
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  4. J Pohl
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  5. B Pyrzynska
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  6. E G Van Meir
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Corresponding author

Correspondence to E G Van Meir.

Additional information

FWK and EGVM designed and interpreted experiments and wrote the manuscript. FWK performed experiments with the help of PS, MR and JP for the MS analyses. BP performed the microarrays and Northern blot. All authors read the manuscript.

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Khwaja, F., Svoboda, P., Reed, M. et al. Proteomic identification of the wt-p53-regulated tumor cell secretome. Oncogene 25, 7650–7661 (2006). https://doi.org/10.1038/sj.onc.1209969

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