Upregulation of mucin glycoprotein MUC1 in the progression to esophageal adenocarcinoma and therapeutic potential with a targeted photoactive antibody-drug conjugate

Mohammed Adil Butt, Hayley Pye, Rehan J. Haidry, Dahmane Oukrif, Saif U. Rehman Khan, Ignazio Puccio, Michael Gandy, Halla Weihe Reinert, Ellie Bloom, Mohammed Rashid, Gokhan Yahioglu, Mahendra P. Deonarain, Rifat Hamoudi, Manuel Rodriguez-Justo, Marco R. Novelli, Laurence B. Lovat

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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Abstract

Background: Mucin glycoprotein 1 (MUC1) is a glycosylated transmembrane protein on epithelial cells. We investigate MUC1 as a therapeutic target in Barrett’s epithelium (BE) and esophageal adenocarcinoma (EA) and provide proof of concept for a light based therapy targeting MUC1.

Results: MUC1 was present in 21% and 30% of significantly enriched pathways comparing BE and EA to squamous epithelium respectively. MUC1 gene expression was x2.3 and x2.2 higher in BE (p=0.0022)

Methods: Gene set enrichment analysis (GSEA) evaluated pathways during BE and EA development and quantified MUC1 gene expression. Immunohistochemistry and flow cytometry evaluated the anti-MUC1 antibody HuHMFG1 in esophageal cells of varying pathological grade. Confocal microscopy examined HuHMFG1 internalization and HuHMFG1 ADCs were created to deliver a MUC1 targeted phototoxic payload.

Conclusions: MUC1 is a promising target in EA. Molecular and light based targeting of MUC1 with a photosensitive ADC is effective in vitro and after development may enable treatment of locoregional tumors endoscopically.
Original languageEnglish
Pages (from-to)25080-25096
Number of pages17
JournalOncotarget
Volume8
Issue number15
DOIs
Publication statusPublished - 15 Feb 2017
Externally publishedYes

Keywords

  • Pharmacology
  • MUC1
  • Esophogeal adenocarcinoma
  • antibody drug conjugate
  • ADC
  • Photodynamic therapy
  • Biomarkers

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