title: Secretome analysis of multiple pancreatic cancer cell lines reveals perturbations of key functional networks.
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.
authors.affiliation: Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schiarea
authors.forename: Graziella
authors.initials: G
authors.lastname: Solinas
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.forename: Graziana Maria
authors.initials: GM
authors.lastname: Scigliuolo
authors.forename: Renzo
authors.initials: R
authors.lastname: Bagnati
authors.forename: Roberto
authors.initials: R
authors.lastname: Fanelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Chiabrando
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena; D019295:Computational Biology; D006801:Humans; D053858:Metabolic Networks and Pathways; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D015398:Signal Transduction; D012984:Software
chemical_list: D009363:Neoplasm Proteins; D020543:Proteome