Distal bile duct carcinomas and pancreatic ductal adenocarcinomas: postulating a common tumor entity

Schmuck, Rosa; Carvalho‐Fischer, Cynthia V. de; Neumann, Christopher C. M.; Pratschke, Johann; Bahra, Marcus

doi:10.1002/cam4.566

Cited by 45 publications

(29 citation statements)

References 94 publications

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“…Their data from a human cancer-profiling array shows that the apelin gene is expressed in a variety of benign and malignant tissues, however, the frequency of gene up regulation was high in carcinomas of the colon, skin and pancreas [11]. They did not see an increase of apelin gene expression in tumors of liver origin, however, carcinomas of the pancreatic head and extrahepatic CCA share similar features, including embryologic origin and several phenotypic characteristics [34]. …”

Section: Discussionmentioning

confidence: 99%

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

et al. 2017

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Purpose Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that is associated with low five-year survival. The apelin receptor (APLNR), which is activated by the apelin peptide, has not been studied in CCA. The purpose of this study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA growth. Methods Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry, and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz-ChA-1 cells were treated with increasing concentrations of apelin and ML221, an APLNR antagonist. Expression of proliferative and angiogenic genes were measured via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice, which were treated with ML221 (150 μg/kg) via tail vein injection. Results Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA proliferation and angiogenesis was inhibited by ML221 treatment. ML221 treatment significantly decreased tumor growth in nu/nu mice. Conclusion The apelin/APLNR axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has the potential to serve as a novel, tumor directed therapy for CCA.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

et al. 2017

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“…Although MUC4 is undetectable in normal bile duct cells, its expression is detectable in the larger bile ducts of intra- and extrahepatic cholangiocarcinomas, as well as ductal adenocarcinomas of the pancreas [88]. …”

Section: Discussionmentioning

confidence: 99%

Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas

et al. 2016

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The cell surface membrane-bound mucin protein MUC4 promotes tumorigenicity, aggressive behavior, and poor outcomes in various types of epithelial carcinomas, including pancreatic, breast, colon, ovarian, and prostate cancer. This review summarizes the theories and findings regarding MUC4 function, and its role in epithelial carcinogenesis. Based on these insights, we developed an outline of the processes and mechanisms by which MUC4 critically supports the propagation and survival of cancer cells in various epithelial organs. MUC4 may therefore be a useful prognostic and diagnostic tool that improves our ability to eradicate various forms of cancer.

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“…Recently, Kim et al [44] demonstrated that plasma THBS2 is a promising diagnostic biomarker for pancreatic cancer. Given the biological similarities of dCCA and pancreatic cancer [45], further evaluation of THBS2 as a potential diagnostic biomarker of dCCA should be encouraged. We have not found any previous study in which the expression of THBS2 in paired lymph node metastases was investigated.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

Byrling

Kristl

et al. 2020

J Transl Med

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Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.

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Distal bile duct carcinomas and pancreatic ductal adenocarcinomas: postulating a common tumor entity

Cited by 45 publications

References 94 publications

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth

Cell membrane-anchored MUC4 promotes tumorigenicity in epithelial carcinomas

Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker

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