Quantitative Expression and Co-Localization of Wnt Signalling Related Proteins in Feline Squamous Cell Carcinoma

Antonio Giuliano, Rebecca Swift, Callum Arthurs, Georgina Marote, Francesca Abramo, Jenny McKay, Calum Thomson, Mariana Beltran, Michael Millar, Simon Priestnall, Jane Dobson, Fernando Costantino-Casas, Terry Petrou, Imelda M McGonnell, Anthony J Davies, Malcolm Weetman, Oliver A Garden, John R Masters, Christopher Thrasivoulou, Aamir Ahmed

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Feline oral squamous cell carcinoma (FOSCC) is an aggressive neoplasm in cats. Little is known about the possible molecular mechanisms that may be involved in the initiation, maintenance and progression of FOSCC. Wnt signalling is critical in development and disease, including many mammalian cancers. In this study, we have investigated the expression of Wnt signalling related proteins using quantitative immunohistochemical techniques on tissue arrays. We constructed tissue arrays with 58 individual replicate tissue samples. We tested for the expression of four key Wnt/ß-catenin transcription targets, namely Cyclin D1 (CCND1 or CD1), FRA1, c-Myc and MMP7. All antibodies showed cross reactivity in feline tissue except MMP7. Quantitative immunohistochemical analysis of single proteins (expressed as area fraction / amount of tissue for normal vs tumor, mean ± SE) showed that the expression of CD1 (3.9 ± 0.5 vs 12.2 ± 0.9), FRA1 (5.5 ± 0.6 vs 16.8 ± 1.1) and c-Myc (5.4 ± 0.5 vs 12.5 ± 0.9) was increased in FOSCC tissue by 2.3 to 3 fold compared to normal controls (p<0.0001). By using a multilabel, quantitative fluorophore technique we further investigated if the co-localization of these proteins (all transcription factors) with each other and in the nucleus (stained with 4',6-diamidino-2-phenylindole, DAPI) was altered in FOSCC compared to normal tissue. The global intersection coefficients, a measure of the proximity of two fluorophore labeled entities, showed that there was a significant change (p < 0.01) in the co-localization for all permutations (e.g. CD1/FRA1 etc), except for the nuclear localization of CD1. Our results show that putative targets of Wnt signalling transcription are up-regulated in FOSCC with alterations in the co-localization of these proteins and could serve as a useful marker for the disease.

Original languageEnglish
Article numbere0161103
JournalPL o S One
Issue number8
Early online date29 Jul 2016
Publication statusPublished - 25 Aug 2016


  • Animals
  • Carcinoma, Squamous Cell/metabolism
  • Cat Diseases/metabolism
  • Cats
  • Cyclin D1/metabolism
  • Gene Expression Regulation, Neoplastic
  • Hydrogen-Ion Concentration
  • Matrix Metalloproteinase 7/metabolism
  • Microtubule-Associated Proteins/metabolism
  • Mouth Neoplasms/metabolism
  • Neoplasm Proteins/genetics
  • Proto-Oncogene Proteins c-myc/metabolism
  • ROC Curve
  • Transcription Factors/metabolism
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway
  • beta Catenin/metabolism


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