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Increased Stromelysin 3 Gene Expression Is Associated with Increased Local Invasiveness in Head and Neck Squamous Cell Carcinomas¹

Centre de Lutte contre le Cancer Paul Strauss, 3, rue de la Porte de l'Hôpital, 67085 [D. M., J. A., R. M., M. E., G. M.]; Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Unité 184 de Biologie Moléculaire et de Génie Génétique de l'INSERM, Institut de Chimie Biologique, Faculté de Médecine, 11, rue Human, 67085 [C. W., M-C. R., P. C., P. B.]; Laboratoire d'Anatomie Pathologique, 29, rue Oberlin, 67000 [A. E.]; Clinique Sainte Barbe, 67000 [G. B.]; and Service d'Anatomie Pathologique Générale, Centre Hospitalier Universitaire, Hôpital de Hautepierre, 1, avenue Molière, 67098 [N. R.]; Strasbourg Cedex, France

Matrix metalloproteinases are believed to play an important role in tumor invasion and metastasis. To examine the expression of the stromelysin 3 (ST3) gene, a new member of the matrix metalloproteinase gene family, 111 head and neck squamous cell carcinomas and 21 metastatic lymph nodes were analyzed by Northern blot. ST3 gene expression was observed in 106 carcinomas and 19 metastatic nodes, but in only 2 of 60 samples of corresponding normal tissue tested in parallel. ST3 RNA, by in situ hybridization, and ST3 protein, by immunohistochemical analysis, were specifically detected in fibroblastic cells immediately surrounding invasive cancer cells. This fibroblastic expression of the ST3 gene is characteristic among the matrix metalloproteinase genes known to be overexpressed in head and neck carcinomas, since stromelysin 2 transcripts were specifically detected in neoplastic cells, and type I collagenase transcripts in both neoplastic cells and stromal fibroblasts. Furthermore, there was a highly significant positive correlation (P < 0.0001) between ST3 RNA levels and local invasiveness by the cancer cells, suggesting that enhanced expression of the ST3 gene may contribute to the neoplastic phenotype in head and neck carcinomas.

¹ Supported by funds from the Ligue Nationale Française contre le Cancer, the Comité du Bas-Rhin de la Ligue contre le Cancer, the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Médicale, the Centre Hospitalier Universitaire Régional, the Association pour la Recherche sur le Cancer, and the Fondation Jeantet.

² To whom requests for reprints should be addressed.

Received 4/28/92. Accepted 10/20/92.

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