Anti-mucin 4 fluorescent antibody brightly targets colon cancer in patient-derived orthotopic xenograft mouse models: A proof-of-concept study for future clinical applications.

Abstract

BACKGROUND:

There is a high rate of positive surgical margins with resection of liver metastases in colorectal cancer (CRC). The present study reports using a fluorescent anti-mucin 4 (MUC4) antibodies to label primary CRC and liver metastases to better visualize tumor margins in mouse models.

METHODS:

Western blotting for MUC4 protein expression of normal colon and CRC tumor lysates was performed. Orthotopic primary and liver metastatic CRC mouse models received anti-MUC4 antibody conjugated to IR800 (MUC4-IR800). Mice were sacrificed and imaged after 48 hours.

RESULTS:

Western blotting demonstrated increased MUC4 expression in a human CRC cell line and patient-derived primary and liver-metastatic CRCs. The LS174T orthotopic primary CRC model tumor to background ratio (TBR) was 2.04 (±0.35). The patient-derived orthotopic xenograft (PDOX) primary CRC model TBR was 2.17 (±0.35). The PDOX liver metastasis model TBR was 1.56 (±0.53).

CONCLUSION:

MUC4-IR800 provided bright labeling of primary and liver tumors in CRC orthotopic mouse models, demonstrating their future clinical potential for margin visualization in fluorescence guided surgery.

• Authors: Michael A Turner, Hannah M Hollandsworth, Siamak Amirfakhri, Thinzar M Lwin, Hiroto Nishino, Nicholas C Neel, Gopalakrishnan Natarajan, Sukhwinder Kaur, Kavita Mallya, Robert M Hoffman, Surinder K Batra, Michael Bouvet
• Journal: American journal of surgery (Am J Surg) Vol. 224 Issue 4 Pg. 1081-1085 (10 2022) ISSN: 1879-1883 [Electronic] United States
• PMID: 35715267 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Topics

• Animals
• Colonic Neoplasms (surgery)
• Disease Models, Animal
• Heterografts
• Humans
• Liver Neoplasms (surgery)
• Mice
• Mice, Nude