Proteomics in pancreatic cancer research

Abstract

In this review, we give an overview of the actual role of proteomic technologies in the study of pancreatic cancers (PCs). We describe PC proteomics on the basis of sample origins, i.e. tissues, body fluids, and PC cell lines. As regards PC tissues, we report the identification of a number of candidate biomarkers of precursor lesions that may allow early diagnosis of this neoplasia. Moreover, we describe cytoskeletal and hypoxia-regulated proteins that confirm the involvement of cytoskeleton modifications and metabolism adaptations in carcinogenesis. We also discuss the most important biomarkers identified by proteomic analysis involved in local invasion and distant metastasis, and in the cross-talk between pancreatic tumor and the surrounding stroma. Furthermore, we report novel candidate biomarkers identified in serum, plasma, and pancreatic juice of cancer patients compared with cancer-free controls. Proteomic alterations in PC cell line models as compared to normal controls and studies on cell lines treated with drugs or new agents to understand their mechanism of pharmacological action or the onset of drug resistance are also presented. Finally, we discuss the recent improvements obtained in classical 2-DE and high-throughput proteomic strategies able to allow the overcoming of relevant proteomic drawbacks.

The Proteome of Postsurgical Pancreatic Juice

“…The spectrum of proteins that the pancreas produces after resection of a malignant tumor may be important because, potentially, it has implications in the postoperative delivery of targeted chemotherapy and radiotherapy. 1 On the other hand, neoadjuvant treatment induces an alteration of the pancreatic proteome. Not surprisingly, nontreated organs seem to have a more thriving production of enzymes implicated in their physiologic function, such as lipase and elastase.…”

“…1 Proteomics can provide key information in the analysis of neoplasm onset, tumor biomarkers, and even chemotherapy effect. 2 The proteome of the normal human pancreatic juice (PJ) has been recently assessed, revealing the presence of multiple proteins related to a diversity of biological processes.…”

Glycoproteins and glycoproteomics in pancreatic cancer

“…A number of proteomics studies in pancreatic cancer have been reported[32-39]. As a subfield of proteomics, glycoproteomics uniquely focuses on analyzing glycosylated proteins to reveal glycoproteome alterations associated with pancreatic cancer.…”

Onconase induces autophagy sensitizing pancreatic cancer cells to gemcitabine and activates Akt/mTOR pathway in a ROS-dependent manner

“…Since the importance of the cytotoxic potential of some RNases belonging to the secretory pancreatic-type RNase super-family definitely increased in the last two decades, we investigated the effects of ONC on cells of human pancreatic adenocarcinoma, which is a particularly aggressive and devastating cancer type [21] characterized by chemoresistance to traditional therapeutic drugs including treatment with the gold standard nucleotide analogue gemcitabine (GEM; 2′,2′-difluoro-2′-deoxycytidine) [22,23]. In particular, we aimed to explore the link between autophagy, ROS, and the antitumor activity of ONC by investigating whether this cytotoxic enzyme may trigger chemosensitivity of pancreatic adenocarcinoma cells to GEM.…”