Study for both the establishment of in vivo model system for the development of salivary mucous cyst and its treatment

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We have examined the content of matrix metalloproteinase-2 and -9 (MMP-2, MMP-9) in luminal fluid of extravasation mucoceles. The luminal fluid showed a high level of MMP activity compared with saliva from Wharton's duct. This result suggests that proteolytic enzymes are involved in the pathogenesis of mucoceles. Thus, based on the above observation, we attempted to construct a cyst-like structure in vivo, and analyzed molecular mechanisms in the development of the lesion. When SV40-immortalized normal human salivary gland cells (NS-SV-DC) were treated with TGF-beta1 at the concentration of 1 ng/ml or 5 ng/ml followed by co-inoculation with Matrigel into the backs of nude mice, they formed large cystic structures containing luminal fluid. Analysis of luminal fluids contained in cystic cavity demonstrated a high MMP activity. Northern blot analysis indicated that expression of TGF-beta1 and MMP-2 mRNAs in cells was greatly enhanced by treatment with TGF-beta1. Furthermore, the development of cyst formation was almost completely inhibited by the addition of TIMP-1 into Matrigel. These findings, therefore, suggest that the in vivo cyst formation by TGF-beta1-treated cells is associated with the continuous induction of MMP-2 activity.