Proteomic Profiling of Pancreatic Cancer for Biomarker Discovery

Chen, Ru; Pan, Sheng; Brentnall, Teresa A.; Aebersold, Ruedi

doi:10.1074/mcp.r500004-mcp200

Cited by 139 publications

(101 citation statements)

References 98 publications

(74 reference statements)

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“…By contrast, annexin 2 and tropomyosin have been much studied and have roles in cytoskeletal organisation and regulation of actin dynamics (Gerke et al, 2005;Gunning et al, 2008). We chose to focus further studies on annexin 2 as, like S100A6 (Vimalachandran et al, 2005) it is also overexpressed in preneoplastic pancreatic lesions (Sitek et al, 2005;Esposito et al, 2006) and is expressed in a similarly high proportion (480%) of invasive cancers (Paciucci et al, 1998;Chen et al, 2005;Ortiz-Zapater et al, 2007). We report here colocalisation of annexin 2 and S100A6 in the plasma membrane of cultured pancreatic cancer cells and pancreatic tumours.…”

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confidence: 99%

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

et al. 2009

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BACKGROUND: High levels of S100A6 have been associated with poor outcome in pancreatic cancer patients. The functional role of S100A6 is, however, poorly understood. METHODS: Immunoprecipitation followed by two-dimensional gel electrophoresis and mass spectrometry were undertaken to identify S100A6 interacting proteins in pancreatic cancer cells. Immunohistochemistry and coimmunofluorescence were performed to examine expression or colocalisation of proteins. siRNA was used to deplete specific proteins and effects on motility were measured using Boyden Chamber and wound healing assays. RESULTS: Our proteomic screen to identify S100A6 interacting proteins revealed annexin 11, annexin 2, tropomyosin b and a candidate novel interactor lamin B1. Of these, annexin 2 was considered particularly interesting, as, like S100A6, it is expressed early in the development of pancreatic cancer and overexpression occurs with high frequency in invasive cancer. Reciprocal immunoprecipitation confirmed the interaction between annexin 2 and S100A6 and the proteins colocalised, particularly in the plasma membrane of cultured pancreatic cancer cells and primary pancreatic tumour tissue. Analysis of primary pancreatic cancer specimens (n ¼ 55) revealed a strong association between high levels of cytoplasmic S100A6 and the presence of annexin 2 in the plasma membrane of cancer cells (P ¼ 0.009). Depletion of S100A6 was accompanied by diminished levels of membrane annexin 2 and caused a pronounced reduction in the motility of pancreatic cancer cells. CONCLUSION: These findings point towards a functional role for S100A6 that may help explain the link between S100A6 expression in pancreatic cancer and aggressive disease.

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S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

et al. 2009

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“…Many studies have reported that pancreatic juice is a rich source of proteins released directly from PC cells, and is an available and useful specimen to identify PC-related antigens (5,8,9). To produce monoclonal antibodies specific for pancreatic juice from PC patients, we immunized mice using subtractive immunization.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have reported that pancreatic juice is a useful specimen to identify PC-related antigens, because it is secreted from the pancreatic ductal lumen from where PC cells arise (5,8,9). Particular antigens in pancreatic juice with specific and/or high expression in PC may be useful to differentiate between benign and malignant disease.…”

Section: Introductionmentioning

confidence: 99%

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Novel monoclonal antibodies against pancreatic juice from pancreatic cancer patients and their possible application in differential diagnosis

Hamabashiri

Daichou²,

Yasumoto³

et al. 2011

Int J Mol Med

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Abstract. Pancreatic cancer (PC) has a poor clinical prognosis with a <10% 5-year survival rate. Because there are no specific biomarkers of PC, it is difficult to detect small PC tumors and most patients are diagnosed at an advanced stage. Specific biomarkers are useful tools for the early detection of cancer. However, PC-related biomarkers, such as CA19-9 lack specificity and sensitivity. In this study, we took an immunological approach to establish novel monoclonal antibodies (mAbs) specific for the pancreatic juice from PC patients, which would be potentially useful in the diagnosis of PC. Mice were immunized by subtractive immunization using mixed pancreatic juices from chronic pancreatitis and PC patients as the tolerogen and the immunogen, respectively. After screening by Western blotting, four mAbs were obtained: 2P-1-2-1, 2P-1-17-1, 6P-3-2-4 and 7P-9-11-6. The mAb 2P-1-2-1 showed reactivity against the tolerogen at 115 and 120 kDa, but only the 120-kDa antigen was also reactive to the immunogen. The mAb 2P-1-17-1 showed an intense smear reactivity at ~150 kDa against the immunogen. Finally, the mAbs 6P-3-2-4 and 7P-9-11-6 showed PC-specific reactivity to the immunogen at >250 kDa and at ~70 kDa, respectively. We propose that investigation of pancreatic juice samples with these mAbs may enable us to perform reliable differential diagnosis of benign and malignant diseases. Furthermore, we demonstrated that subtractive immunization is a useful method for producing mAbs specific for the pancreatic juice from PC patients.

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“…Most patients die within 12 months and only 4% survive for 5 years after diagnosis [1,2]. In the past decade, various mass spectrometry-based approaches have been applied to investigate the proteomes of diseased and normal samples from pancreatic tissues, juice, cell lines, and serum, with the goals of dissecting the abnormal signaling pathways underlying oncogenesis and identifying new biomarkers [3][4][5][6][7][8][9][10][11][12][13]; however, the description of the content of phosphoproteins in pancreatic cancer cells were limited. Since this information archive represents many of the new drug targets for kinase-based inhibitors, it is of critical importance to characterize this molecular information source.…”

Section: Introductionmentioning

confidence: 99%

Phosphoproteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Differential Phosphorylation of Cell Adhesion, Cell Junction and Structural Proteins

Zhou

Capello²,

Fredolini

et al. 2011

JPB

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Proteomic Profiling of Pancreatic Cancer for Biomarker Discovery

Cited by 139 publications

References 98 publications

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

Novel monoclonal antibodies against pancreatic juice from pancreatic cancer patients and their possible application in differential diagnosis

Phosphoproteomic Analysis of Pancreatic Ductal Adenocarcinoma Cells Reveals Differential Phosphorylation of Cell Adhesion, Cell Junction and Structural Proteins

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