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

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 radio...

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Main Authors: Ashleigh Hull, Yanrui Li, Dylan Bartholomeusz, William Hsieh, Samantha Escarbe, Andrew Ruszkiewicz, Eva Bezak
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/1/61
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author Ashleigh Hull
Yanrui Li
Dylan Bartholomeusz
William Hsieh
Samantha Escarbe
Andrew Ruszkiewicz
Eva Bezak
author_facet Ashleigh Hull
Yanrui Li
Dylan Bartholomeusz
William Hsieh
Samantha Escarbe
Andrew Ruszkiewicz
Eva Bezak
author_sort Ashleigh Hull
collection DOAJ
description 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.
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spelling doaj.art-925c065710694384adc8c36adc8f36022023-11-21T02:48:47ZengMDPI AGCancers2072-66942020-12-011316110.3390/cancers13010061The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide TherapyAshleigh Hull0Yanrui Li1Dylan Bartholomeusz2William Hsieh3Samantha Escarbe4Andrew Ruszkiewicz5Eva Bezak6Cancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, AustraliaCancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, AustraliaDepartment of PET, Nuclear Medicine & Bone Densitometry, SA Medical Imaging, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaCancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, AustraliaCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA 5000, AustraliaCancer Research Institute and Allied Health and Human Performance Academic Unit, University of South Australia, Adelaide, SA 5000, AustraliaImprovements 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.https://www.mdpi.com/2072-6694/13/1/61pancreatic cancermucin 1targeted radionuclide therapytextural analysis
spellingShingle Ashleigh Hull
Yanrui Li
Dylan Bartholomeusz
William Hsieh
Samantha Escarbe
Andrew Ruszkiewicz
Eva Bezak
The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
Cancers
pancreatic cancer
mucin 1
targeted radionuclide therapy
textural analysis
title The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
title_full The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
title_fullStr The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
title_full_unstemmed The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
title_short The Expression Profile and Textural Characteristics of C595-Reactive MUC1 in Pancreatic Ductal Adenocarcinoma for Targeted Radionuclide Therapy
title_sort expression profile and textural characteristics of c595 reactive muc1 in pancreatic ductal adenocarcinoma for targeted radionuclide therapy
topic pancreatic cancer
mucin 1
targeted radionuclide therapy
textural analysis
url https://www.mdpi.com/2072-6694/13/1/61
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