Secretome Analysis of Multiple Pancreatic Cancer Cell Lines Reveals Perturbations of Key Functional Networks
- 5 August 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Proteome Research
- Vol. 9 (9), 4376-4392
- https://doi.org/10.1021/pr1001109
Abstract
The cancer secretome is a rich repository in which to mine useful information for both cancer biology and clinical oncology. To help understand the mechanisms underlying the progression of pancreatic cancer, we characterized the secretomes of four human pancreatic ductal adenocarcinoma (PDAC) cell lines versus a normal counterpart. To this end, we used a proteomic workflow based on high-confidence protein identification by mass spectrometry, semiquantitation by a label-free approach, and network enrichment analysis by a system biology tool. Functional networks significantly enriched with PDAC-dysregulated proteins included not only expected alterations within key mechanisms known to be relevant for tumor progression (e.g., cell−cell/cell−matrix adhesion, extracellular matrix remodeling, and cytoskeleton rearrangement), but also other extensive, coordinated perturbations never observed in pancreatic cancer. In particular, we highlighted perturbations possibly favoring tumor progression through immune escape (i.e., inhibition of the complement system, deficiency of selected proteasome components within the antigen-presentation machinery, and inhibition of T cell cytoxicity), and a defective protein folding machinery. Among the proteins found concordantly oversecreted in all of our PDAC cell lines, many are reportedly overexpressed in pancreatic cancer (e.g., CD9 and Vimentin), while others (PLOD3, SH3L3, PCBP1, and SFRS1) represent novel PDAC-secreted proteins that may be worth investigating.Keywords
This publication has 79 references indexed in Scilit:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs): Positive and negative regulators in tumor cell adhesionSeminars in Cancer Biology, 2010
- Exosomal Secretion of Cytoplasmic Prostate Cancer Xenograft-derived ProteinsMolecular & Cellular Proteomics, 2009
- Multiple-Approaches to the Identification and Quantification of Cytochromes P450 in Human Liver Tissue by Mass SpectrometryJournal of Proteome Research, 2008
- Label-free Quantitative Analysis of One-dimensional PAGE LC/MS/MS ProteomeMolecular & Cellular Proteomics, 2008
- Cancer-related inflammationNature, 2008
- Identification of Differentially Secreted Biomarkers Using LC-MS/MS in Isogenic Cell Lines Representing a Progression of Breast CancerJournal of Proteome Research, 2007
- Signaling-dependent and coordinated regulation of transcription, splicing, and translation resides in a single coregulator, PCBP1Proceedings of the National Academy of Sciences of the United States of America, 2007
- Protein folding and misfoldingNature, 2003
- Cancer immunoediting: from immunosurveillance to tumor escapeNature Immunology, 2002
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976