Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a <i>Cdx2-Cre</i...

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Main Authors: Michael A. Turner, Kristin E. Cox, Shanglei Liu, Nicholas Neel, Siamak Amirfakhri, Hiroto Nishino, Mojgan Hosseini, Joshua A. Alcantara, Amer Ali Abd El-Hafeez, Thinzar M. Lwin, Kavita Mallya, Joseph R. Pisegna, Satish K. Singh, Pradipta Ghosh, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Current Issues in Molecular Biology
Subjects:
Online Access:https://www.mdpi.com/1467-3045/45/4/219
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author Michael A. Turner
Kristin E. Cox
Shanglei Liu
Nicholas Neel
Siamak Amirfakhri
Hiroto Nishino
Mojgan Hosseini
Joshua A. Alcantara
Amer Ali Abd El-Hafeez
Thinzar M. Lwin
Kavita Mallya
Joseph R. Pisegna
Satish K. Singh
Pradipta Ghosh
Robert M. Hoffman
Surinder K. Batra
Michael Bouvet
author_facet Michael A. Turner
Kristin E. Cox
Shanglei Liu
Nicholas Neel
Siamak Amirfakhri
Hiroto Nishino
Mojgan Hosseini
Joshua A. Alcantara
Amer Ali Abd El-Hafeez
Thinzar M. Lwin
Kavita Mallya
Joseph R. Pisegna
Satish K. Singh
Pradipta Ghosh
Robert M. Hoffman
Surinder K. Batra
Michael Bouvet
author_sort Michael A. Turner
collection DOAJ
description Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a <i>Cdx2-Cre</i> transgene (<i>CPC-APC</i>) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (<i>p</i>-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in <i>CPC-APC</i> mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.
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spelling doaj.art-0a7999883a40427280a4ee5a75ae457b2023-11-17T18:47:57ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452023-04-014543347335810.3390/cimb45040219Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon CancerMichael A. Turner0Kristin E. Cox1Shanglei Liu2Nicholas Neel3Siamak Amirfakhri4Hiroto Nishino5Mojgan Hosseini6Joshua A. Alcantara7Amer Ali Abd El-Hafeez8Thinzar M. Lwin9Kavita Mallya10Joseph R. Pisegna11Satish K. Singh12Pradipta Ghosh13Robert M. Hoffman14Surinder K. Batra15Michael Bouvet16Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADepartment of Pathology, University of California San Diego, La Jolla, CA 92037, USADepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USADepartment of Surgical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USADepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Gastroenterology, VA Los Angeles Healthcare System, Los Angeles, CA 90073, USAMedical Service, Section of Gastroenterology, VA Boston Healthcare System, Boston, MA 02130, USADepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92037, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USADepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198, USADivision of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA 92037, USAPoor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a <i>Cdx2-Cre</i> transgene (<i>CPC-APC</i>) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 μg PBR was 1.70 (±0.56); the mean 50 μg PBR was 2.64 (±0.97); the mean 100 μg PBR was 3.32 (±1.33); and the mean 150 μg PBR was 3.38 (±0.87). The mean PBR of the dye-only control was 2.22 (±1.02), significantly less than the 150 μg arm (<i>p</i>-value 0.008). The present study demonstrates the ability of fluorescent anti-MUC5AC antibodies to specifically target and label colonic polyps containing high-grade dysplasia and intramucosal adenocarcinoma in <i>CPC-APC</i> mice. This technology can potentially improve the detection rate and decrease the miss rate of advanced colonic neoplasia and early cancer at colonoscopy.https://www.mdpi.com/1467-3045/45/4/219colorectal cancerpolypsfluorescencefluorescence labelingmucindetection
spellingShingle Michael A. Turner
Kristin E. Cox
Shanglei Liu
Nicholas Neel
Siamak Amirfakhri
Hiroto Nishino
Mojgan Hosseini
Joshua A. Alcantara
Amer Ali Abd El-Hafeez
Thinzar M. Lwin
Kavita Mallya
Joseph R. Pisegna
Satish K. Singh
Pradipta Ghosh
Robert M. Hoffman
Surinder K. Batra
Michael Bouvet
Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
Current Issues in Molecular Biology
colorectal cancer
polyps
fluorescence
fluorescence labeling
mucin
detection
title Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
title_full Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
title_fullStr Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
title_full_unstemmed Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
title_short Specific Targeting and Labeling of Colonic Polyps in <i>CPC-APC</i> Mice with Mucin 5AC Fluorescent Antibodies: A Model for Detection of Early Colon Cancer
title_sort specific targeting and labeling of colonic polyps in i cpc apc i mice with mucin 5ac fluorescent antibodies a model for detection of early colon cancer
topic colorectal cancer
polyps
fluorescence
fluorescence labeling
mucin
detection
url https://www.mdpi.com/1467-3045/45/4/219
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