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.

Autor: Turner MA; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: maturner@health.ucsd.edu., Hollandsworth HM; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: hhollandsworth@health.ucsd.edu., Amirfakhri S; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: siamirfakhri@health.ucsd.edu., Lwin TM; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: thinzar_lwin@DFCI.Harvard.edu., Nishino H; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: hnishino@kuhp.kyoto-u.ac.jp., Neel NC; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA. Electronic address: nneel@health.ucsd.edu., Natarajan G; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: g.natarajan@unmc.edu., Kaur S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: skaur@unmc.edu., Mallya K; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: kmallya@unmc.edu., Hoffman RM; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; AntiCancer, Inc., 7917 Ostrow St, San Diego, CA, 92111, USA. Electronic address: all@anticancer.com., Batra SK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: sbatra@unmc.edu., Bouvet M; Department of Surgery, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037, USA; VA San Diego Healthcare System, 3350 La Jolla Village Dr., San Diego, CA, 92161, USA. Electronic address: mbouvet@health.ucsd.edu.
Jazyk: angličtina
Zdroj: American journal of surgery [Am J Surg] 2022 Oct; Vol. 224 (4), pp. 1081-1085. Date of Electronic Publication: 2022 May 31.
DOI: 10.1016/j.amjsurg.2022.05.036
Abstrakt: 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.
Competing Interests: Declaration of competing interest RMH is a non-salaried affiliate of AntiCancer Inc. which uses PDOX models for contract research. All other authors have nothing to disclose.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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