Stromelysin-3 expression is an early event in human oral tumorigenesis

Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis.