Expression of Snail is associated with myofibroblast phenotype development in oral squamous cell carcinoma.
Snail is a regulator of epithelial-mesenchymal transition (EMT) and considered crucial to carcinoma metastasis, myofibroblast transdifferentiation, and fibroblast activation. To investigate the role of Snail in oral squamous cell carcinoma (OSCC), its immunohistochemical expression was analysed in 129 OSCC samples and correlated to nodal metastasis, histological grade, E-cadherin, and alpha smooth-muscle-actin (alpha SMA). The results were compared to findings in 23 basal cell carcinomas (BCC). Additionally, the influence of TGF beta 1 and EGF on Snail, E-cadherin, vimentin, and alpha SMA expression was analysed in two OSCC cell lines. As a result, Snail-positive cells were mainly found in the stroma of the OSCC invasive front without statistically significant correlation to histological grade or nodal metastasis. Snail was co-localised to alpha SMA but not to E-cadherin or cytokeratin and showed a significant correlation to the loss of membranous E-cadherin. All BCCs were Snail negative. In OSCC culture, the growth-factor-mediated EMT-like phenomenon was accompanied by alpha SMA down-regulation. In summary, Snail expression in OSCC is a stromal phenomenon associated with the myofibroblast phenotype and not related to growth-factor-mediated transdifferentiation of the carcinoma cells themselves. Consequently, Snail immunohistochemistry cannot contribute to the prediction of the metastatic potential. Furthermore, stromal Snail expression is suggested to be the result of mutual paracrine interaction of fibro-/myofibroblasts and dedifferentiated carcinoma cells leading to the generation of a special type of carcinoma-associated fibroblasts.
Franz
Marcus
M
Clinic of Internal Medicine I, University Hospital Jena, 07740, Jena, Germany.
Spiegel
Karin
K
Umbreit
Claudia
C
Richter
Petra
P
Codina-Canet
Carolina
C
Berndt
Angela
A
Altendorf-Hofmann
Annelore
A
Koscielny
Sven
S
Hyckel
Peter
P
Kosmehl
Hartwig
H
Virtanen
Ismo
I
Berndt
Alexander
A
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D014408:Biomarkers, Tumor; D015820:Cadherins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D004815:Epidermal Growth Factor; D007633:Keratins