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: 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
Rok vydání: 2022
Předmět:
Zdroj: American journal of surgery, vol 224, iss 4
Am J Surg
ISSN: 0002-9610
DOI: 10.1016/j.amjsurg.2022.05.036
Popis: 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.
Databáze: OpenAIRE
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