Expression of 72 kilodalton and 92 kilodalton type IV collagenase in malignant fibrous histiocytomas and dermatofibromas.

BACKGROUND

In previous studies, it has been shown that the stromal cells of epithelial tumors are capable of synthesizing 72 and 92 kilodalton (kd) type IV collagenase mRNA. The mRNA synthesis of these collagenases in mesenchymal tumors has not been extensively studied, however. This study was undertaken to explore the synthesis of 72 and 92 kd type IV collagenase mRNAs in malignant and benign fibrous histiocytomas and its correlation with the known biologic behavior of these tumors.

EXPERIMENTAL DESIGN

The synthesis of 72 kd and 92 kd type IV collagenase mRNA was studied in 10 malignant fibrous histiocytomas (MFHs) and 7 dermatofibromas using in situ hybridization methods. The tumors were also studied with a commercial monoclonal antibody to the 72 kd type IV collagenase. Additionally, three dermatofibromas were studied with an antibody to the 92 kd type IV collagenase. The media of three cell lines (MFH, dermatofibroma and skin fibroblast cell line) were also analyzed by zymography assay.

RESULTS

The results revealed mRNA for the 72 kd and 92 kd collagenases in tumor cells of both MFHs and dermatofibromas. Also intracytoplasmic immunoreactivity for the 72 kd type IV collagenase could be seen in all the tumors. In the zymography assay, 72 kd type IV collagenase activity was detected in the culture media of all the cell lines tested, but activity for the 92 kd enzyme was only seen in the MFH. However, immunoreactivity for the antibody to the 92 kd type IV collagenase was also seen in dermatofibromas.

CONCLUSIONS

The findings indicate that MFHs and dermatofibromas produce type IV collagenases. The synthesis of the mRNAs for both 72 kd and 92 kd type IV collagenase was quantitatively similar in MFHs and dermatofibromas indicating that there is no correlation between the biologic behavior of the tumors and the synthesis of these substances. Therefore, additional factors other than synthesis of type IV collagenases by tumor cells, must be involved in the process of spread and invasion of tumor cells into the neighbouring tissues.