Background: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.
Methods: Samples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.
Results: All cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.
Conclusions: Our work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.
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http://dx.doi.org/10.1016/j.pan.2020.08.004 | DOI Listing |
J Gastroenterol
January 2025
Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.
Background: To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.
Methods: Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP).
Mol Carcinog
January 2025
Center for Pancreatic Cancer Research, The South China University of Technology School of Medicine, Guangzhou, Guangdong, China.
Pancreatic cancer is a highly lethal malignancy with few effective treatment options. Connexin 31 (Cx31) is a membrane protein capable of forming hexameric channels to facilitate the exchange of metabolites and signaling molecules. Yet, the contribution of Cx31 to the onset and progression of pancreatic cancer remains to be understood.
View Article and Find Full Text PDFAbdom Radiol (NY)
December 2024
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, largely due to its poor five-year survival rate and frequent late-stage diagnosis. A significant barrier to early detection even in high-risk cohorts is that the pancreas often appears morphologically normal during the pre-diagnostic phase. Yet, the disease can progress rapidly from subclinical stages to widespread metastasis, undermining the effectiveness of screening.
View Article and Find Full Text PDFNat Commun
December 2024
Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated fibroblasts and integrins have been proposed as targets for imaging of pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics and proteomics of human surgical samples are applied to select PDAC targets. We find that selected cancer cell surface markers are spatially correlated and provide specific cancer localization, whereas the spatial correlation between cancer markers and immune-related or fibroblast markers is low.
View Article and Find Full Text PDFPancreatology
December 2024
Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address:
Background: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has become essential for diagnosing pancreatic ductal adenocarcinoma (PDAC) and is increasingly utilized for comprehensive genome profiling (CGP) to advance precision medicine. This systematic review and meta-analysis assess the feasibility and clinical utility of EUS-TA samples for CGP in PDAC.
Methods: We conducted a thorough systematic literature search in PubMed, EMBASE, and the Cochrane Library up to October 2023.
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