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Localization of Messenger RNA for M_r 72,000 and 92,000 Type IV Collagenases in Human Skin Cancers by in Situ Hybridization¹

Finsen Laboratory [C. P., K. D.] and Department of Pathology [E. R.], Rigshospitalet, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark, and Biocenter and Department of Biochemistry, University of Oulu, SF-90570 Oulu, Finland [P. H., T. H., K. T.]

We have examined the expression of 2 type IV collagen degrading enzymes (M_r 72,000 and 92,000 type IV collagenases) in human skin cancer by in situ hybridization. In all cases of infiltrating carcinomas of squamous cell (9 of 9) and basal cell (5 of 5) types, messenger RNA for the M_r 72,000 type IV collagenase was present in numerous fibroblasts. These were especially abundant in the stroma adjacent to the invasive tumor nodules. Malignant cells were negative for mRNA for the M_r 72,000 enzyme in all cases as were all other epithelial as well as endothelial cells. mRNA for the M_r 92,000 type IV collagenase was present in all 9 squamous cell and in 3 of the 5 basal cell carcinomas. In all these cases, a subpopulation of tissue macrophages was found to be positive, while malignant cells showed a signal for M_r 92,000 type IV collagenase in 6 of the squamous cell carcinomas but in none of the basal cell carcinomas. In all cases, the signal for this mRNA was confined to cells located at the tumoral/stromal interface or in the close vicinity of tumor nodules. No mRNA for any of the 2 collagenases was detected in 3 biopsies of normal skin.

In vitro studies have indicated that collagenases are involved in the degradation of the extracellular matrix during cancer invasion. The present findings are consistent with such a role of the M_r72,000 and 92,000 type IV collagenases in squamous and basal cell carcinomas in situ. The findings also demonstrate that degradative enzymes are not necessarily produced by the malignant cells themselves but may be generated by induction or recruitment of nonmalignant stromal cells.

¹ This work was supported financially by the Danish Biotechnology Programme, the Danish Cancer Society, the Danish Medical Research Council, the Finnish Cancer Society, the Finnish Cancer Institute, the Academy of Finland, and the Harboe Foundation.

² To whom requests for reprints should be addressed, at: Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark.

Received 8/23/91. Accepted 12/ 5/91.

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