The Proteome of Pancreatic Cancer‐Derived Exosomes Reveals Signatures Rich in Key Signaling Pathways

Abstract

Exosomes are membrane‐bound vesicles that traffic small molecular cargos. These cargos participate in cell–cell communication and contribute to the pathogenesis of many disease including cancer. How these mechanisms contribute to communication within the pancreatic adenocarcinoma (PDAC) microenvironment and how they contribute to PDAC biology are poorly understood. Performed in this study are comprehensive, quantitative comparisons of the proteomes of three PDAC cell lines to those of the exosomes they produce. Approximately 35% of whole cell proteins sort into exosomes. Analysis of composition of microbiomes (ANCOM) determined a cluster of 98 enriched pancreatic cancer exosome core proteins (ePC‐ECPs). Further, these proteins are predicted by ingenuity pathway analysis (IPA) as actively involved in signaling pathways regulating cell death and survival, cellular movement, and cell‐to‐cell signaling and interaction in particular (top three p‐value significant pathways). Significant enrichment of canonical pathways of acute phase response signaling (inflammatory response signaling pathways) and FXR and RXR activation in biosynthetic pathways are also predicted; 97 ePC‐ECPs are associated with cancer and among them, 34 are specifically associated with PDAC. In conclusion, exosomes from PDAC are enriched with cancer‐associated signaling proteins. Further assessment of these proteins as PDAC biomarkers or therapeutic targets is warranted.

The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells

“…We analyzed by western blotting the extracellular expression level of vimentin (VIM) in CM-mock, CM-R273H, and CM-R175H of AsPC-1 cells, confirming the hyper-secretion of VIM induced by both mutant p53 isoforms in order to validate mass spectrometry data ( Figure S3 ). We have further investigated whether these 15 proteins were already identified in PDAC-derived exosomes and seven of them, namely PROCR, TIMP1, EZR, PSAP, VIM, CLSTN1 and CFL1, were detected in the proteome of pancreatic cancer exosomes using mass spectrometry [ 38 ], which suggests their roles as key signaling molecules.…”

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

“…Exosomes transport a distinct molecular cargo of proteins and nucleic acids (mRNA, miRNA and genomic dNA) in peripheral blood (PB) and other bio-fluids (e.g., urine and saliva), and are recognized as relevant for the diagnosis and prognosis of certain pathologies, particularly solid tumors. Several studies have demonstrated that the proteins and nucleic acids contained within the exosomes of cancer patients can be isolated and identified as exosomal markers associated with cancer evolution (1)(2)(3)(4)(5).…”

Comparative evaluation of methods for isolating small extracellular vesicles derived from pancreatic cancer cells

“…Conventional differential ultracentrifugation has been widely used, but may not be able to remove all contaminants [1,2]. To obtain sEVs with small size, 0.22 μm filtration membranes were used in some studies to remove the microvesicles [3,4], but the filtration membrane could not remove protein contaminants, which may mislead the study results [5,6]. The International Society for Extracellular Vesicles (ISEV) advised that the qualities of EV from different isolation methods were different [7].…”