EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat.OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner.Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.Oral squamous cancer cell carcinoma (OSCC) ranks among the top ten most frequently cancers, and 500 000 people per year are world widely diagnosed [1]. OSCC is highly invasive with bad prognosis; despite the recent advances in cancer therapy, the 5-year survival rate of patients has remained at < 50% [2]. Little is known about of the molecular events that govern OSCC initiation, progression and metastasis. Development of OSCC is a complex and multistep process, with transformation from oral premalignant dysplastic lesion to OSCC. Progression is generally known to involve the intervention of proteinases [3-5]. Extracellular matrix metalloproteinase inducer (EMMPRIN/CD147), a membrane glycoprotein greatly enriched on the surface of tumor cells, is mainly known for its ability to increase the synthesis of MMPs in tumor cells and in the neighbouring stromal cells, such as fibroblasts and endothelial cells [6-1