Illustrations
Figure 1
TG3 is differentially expressed in skin cancer based on tissue micro-array: H&E staining and immunohistochemical analysis of Ki67 and TG3 expression in (A ) normal skin (n = 10), (B ) cutaneous melanoma samples (n = 10), and (C ) cutaneous squamous cell carcinoma (n = 39) (two representative cases of poorly- and well-differentiated tumours are shown). D ) H&E staining and immunohistochemical analysis of Ki67, TG3, and Ep-CAM expression in cutaneous basal cell carcinoma (n = 13) (two representative cases with low and high levels of TG3 expression are shown).
Figure 1
Figure 2
TG3 is highly expressed in Ep-CAM+ basal cell carcinoma. A ) H&E staining and immunohistochemical analysis of Ki67, TG3, and Ep-CAM expression in cutaneous basal cell carcinoma (n = 6). B ) Table showing the median H-score for TG3 and fold change in TG3 expression in tumour samples relative to normal skin. C ) Violin plot showing TG3 H-score distribution in the samples of normal skin and skin cancer from (B ).
Figure 2
Figure 3
TGM3 is uniquely overexpressed in BCC relative to other TGs and its substrates. A ) Violin plot showing relative mRNA expression of TGM3 in normal and skin cancer samples from GSE7553. B ) Violin plot showing relative mRNA expression levels of TGM1, TGM5, LOR, and IVL in normal and BCC samples from GSE7553. C ) Immunofluorescence analysis of TG3 and LOR expression in a case of BCC (the yellow dashed line separates the epidermis and dermis and white dashed lines indicate the tumour regions).
Figure 3
Figure 4
Differentiation-correlated profile of TGM3 expression is lost in BCC, but not in SCC. A ) Heatmaps showing the correlation of expression between TGM1, TGM3, TGM5, LOR, and IVL in normal skin and different types of skin cancer based on the gene array, GSE7553. B ) Gene ontology analysis showing the top 300 genes co-expressed with either LOR or TGM3 in melanoma, BCC, and SCC based on the gene array, GSE7553. Pearson's correlation R > +0.50.
Figure 4
Auteurs
1 Department of Experimental Medicine, TOR, University of Rome “Tor Vergata”, 00133 Rome, Italy
2 Istituto Dermopatico dell’Immacolata-IRCCS, 00163 Rome, Italy
3 Department of Dermatology, University of Rome “Tor Vergata”, 00133 Rome, Italy
4 MRC-Toxicology Unit, University of Cambridge, UK
Background
Transglutaminase 3 (TG3) belongs to a family of Ca2+ -dependent enzymes which catalyse protein crosslinking. TG3 is important for proper development of the skin and hair shaft, and knock-out mice for the Tgm3 gene are sensitive to UVB-induced photodamage due to aberrations in cornified envelope formation. Loss of TG3 is reported in head and neck and oesophageal squamous cell carcinoma, yet, its expression in skin cancer has not been studied.