The involvement of a disintegrin and metalloprotease domain (ADAM)-17 on the cancer invasion was investigated in oral squamous cell carcinoma (OSCC) cells. TNF alpha induced the conversion from the proform of ADAM-17 to its mature form time-dependently. TNF alpha also cleaved CD44 to its small fragments, as observed by a Western blot analysis. The transfection of ADAM-17 siRNA partially suppressed the expression of ADAM-17 as well as the cleavage of CD44. On the other hand, TNF alpha activated a transcription factor NF-kappa B in OSCC cells, while NBD peptide, an NF-kappa B inhibitor, inhibited the ADAM-17 maturation, thus suggesting that NF-kappa B is involved in ADAM-17 maturation. Moreover, an in vitro invasion assay revealed that both ADAM-17 siRNA and NBD peptides strongly suppressed the TNF alpha-induced invasion of OSCC cells through the matrix. In conclusion, ADAM-17 plays an important role in cancer invasion probably through CD44 cleavage. (c) 2007 Elsevier Inc. All rights reserved.