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

Abstract

BACKGROUNDS:

An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

• Authors: Géraldine Lescaille, Suzanne Menashi, Bénédicte Cavelier-Balloy, Farah Khayati, Cathy Quemener, Marie Pierre Podgorniak, Benyoussef Naïmi, Fabien Calvo, Céleste Lebbe, Samia Mourah
• Journal: BMC cancer (BMC Cancer) Vol. 12 Pg. 115 (Mar 23 2012) ISSN: 1471-2407 [Electronic] England
• PMID: 22443116 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neoplasm Proteins
• Basigin
• Urokinase-Type Plasminogen Activator

Topics

• Basigin (physiology)
• Blotting, Western
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Disease Progression
• Humans
• Immunohistochemistry
• Mouth Neoplasms (metabolism, pathology)
• Neoplasm Invasiveness (pathology)
• Neoplasm Proteins (physiology)
• Precancerous Conditions (metabolism)
• Real-Time Polymerase Chain Reaction
• Up-Regulation
• Urokinase-Type Plasminogen Activator (metabolism)