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Article

The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy

1
Cancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, Australia
2
Department of PET, Nuclear Medicine & Bone Densitometry, SA Medical Imaging, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
3
Adelaide Medical School, The University of Adelaide, Adelaide, SA 5000, Australia
4
Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, Australia
5
Division of Anatomical Pathology, SA Pathology, Adelaide, SA 5000, Australia
6
Department of Physics, The University of Adelaide, Adelaide, SA 5000, Australia
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(1), 61; https://doi.org/10.3390/cancers13010061
Received: 3 November 2020 / Revised: 16 December 2020 / Accepted: 22 December 2020 / Published: 28 December 2020
Pancreatic ductal adenocarcinoma (PDAC) is a cancer of low survival needing novel treatment approaches such as targeted therapies. If a target is overexpressed on PDAC cells but has minimal expression on normal cells, it is considered a good candidate for targeted therapy. Identifying targets with this expression pattern can help to optimise targeted therapies to be therapeutically effective without compromising on tolerability. The aim of this study was to assess the expression of the MUC1 receptor using the C595 antibody. We performed a series of cell line and tissue studies to identify if the expression of the MUC1 receptor changes between different pancreatic pathologies, including PDAC and normal pancreatic tissue. We found that the MUC1 receptor is both overexpressed and more uniformly expressed in PDAC compared to the other tissue types assessed. This indicates that the MUC1 receptor is a feasible target for targeted therapies of PDAC.
Improvements in the prognosis of pancreatic ductal adenocarcinoma (PDAC) rely on the development of effective treatments to target advanced disease. Mucin 1 (MUC1) is a transmembrane glycoprotein which is involved in the metastatic progression of PDAC and is a receptor-of-interest for targeted radionuclide therapy. The aim of this study was to determine the feasibility of MUC1-based targeted radionuclide therapy for PDAC, by evaluating the expression profile of MUC1 in different pancreatic cells and tissues using the C595 antibody. MUC1 expression was evaluated in four PDAC cell lines (PANC-1, BxPC-3, CAPAN-1 and AsPC-1) using flow cytometry and immunocytochemistry. Immunohistochemistry was performed on primary and metastatic PDAC, pancreatitis, pancreatic intra-epithelial neoplasia and normal pancreatic tissue samples to identify potential changes in C595-reactive MUC1 expression across different disease groups. C595-reactive MUC1 expression was found to varying degrees in the cell lines (11.5–93.1%). A pixel analysis of the immunohistochemical staining demonstrated highest MUC1 expression in primary PDAC tissue (mean pixel value of 205.4), followed by other pancreatic cancer types (204.9), pancreatic intra-epithelial neoplasia (203.8), metastatic PDAC (201.5), chronic pancreatitis (198.1) and normal pancreatic tissue (191.4). The increased expression in malignant tissues and reduced expression in benign tissues indicate that C595-reactive MUC1 is a potential target for targeted radionuclide therapy of PDAC. View Full-Text
Keywords: pancreatic cancer; mucin 1; targeted radionuclide therapy; textural analysis pancreatic cancer; mucin 1; targeted radionuclide therapy; textural analysis
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MDPI and ACS Style

Hull, A.; Li, Y.; Bartholomeusz, D.; Hsieh, W.; Escarbe, S.; Ruszkiewicz, A.; Bezak, E. The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy. Cancers 2021, 13, 61. https://doi.org/10.3390/cancers13010061

AMA Style

Hull A, Li Y, Bartholomeusz D, Hsieh W, Escarbe S, Ruszkiewicz A, Bezak E. The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy. Cancers. 2021; 13(1):61. https://doi.org/10.3390/cancers13010061

Chicago/Turabian Style

Hull, Ashleigh; Li, Yanrui; Bartholomeusz, Dylan; Hsieh, William; Escarbe, Samantha; Ruszkiewicz, Andrew; Bezak, Eva. 2021. "The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy" Cancers 13, no. 1: 61. https://doi.org/10.3390/cancers13010061

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