HUMAN COLLAGENASE-3 IS EXPRESSED IN MALIGNANT SQUAMOUS EPITHELIUM OF THE SKIN

Go-expression of several members of the matrix metalloproteinase (MMP) family is a characteristic of human carcinomas, To investigate the ro le of the recently cloned collagenase-3 (MMP-13) in epidermal tumors, me studied samples representing malignant (basal and squamous cell car cinoma, Pager's disease), pre-malignant (Bowen's disease, solar kerato sis), and benign (keratoacanthoma, seborrheic keratosis, linear epider mal nevus) tumors, Basal cell carcinomas expressed collagenase-3 mRNA in focal areas of keratinized cells, the squamous differentiation of w hich was confirmed by positive immunostaining for involucrin, Apoptosi s was observed in central parts of these foci, In squamous cell carcin omas, collagenase-3 expression was detected at the epithelial tumor fr ont and less frequently in the surrounding stromal cells, Collagenase- 3 mRNA co-localized with immunostaining for laminin-5, an adhesion mol ecule suggested to participate in the migration of tumor cells, The pr e-malignant and benign tumors were mostly negative for collagenase-3, Stromelysin-1, a potential activator of latent collagenases, was frequ ently expressed by stromal cells surrounding the malignant tumors, and the two MMPs occasionally co-localized in keratotic foci. Our results demonstrate that in basal cell carcinomas, expression of collagenase- 3 is associated with terminal differentiation of epithelial cells, Fur thermore, the gene is activated during skin carcinogenesis, and we sug gest a role for collagenase-3 in degradation of the extracellular matr ix associated with malignant epithelial growth.