Gelatinase A and membrane-type 1 matrix metalloproteinase mRNA: Expressed in adrenocortical cancers but not in adenomas

In an attempt to understand the mechanism behind the invasion and metastasi s in adrenocortical cancer we performed mRNA in situ hybridization on 30 tu mors for three matrix metalloproteinases (MMPs): gelatinase A, membrane typ e 1 matrix metalloproteinase (MT1-MMP), and collagenase-3, All are known to participate in the invasion and metastasis of other tumor forms by degradi ng the extracellular matrix. Thirteen of sixteen cancers, but only one of f ourteen benign lesions showed expression of gelatinase A, which was localiz ed in stromal cells, MT1-MMP is thought to assist in tumor invasion and met astasis by activating the zymogen gelatinase A. Of 14 malignant tumors anal yzed, 12 showed MT1-MMP mRNA expression, which in 7 cases was detected in b oth neoplastic and stromal cells. The benign tumors showed MT1-MMP expressi on in only 3 of 11 cases, and it was restricted to tumor cells. Fourteen tu mors (11 cancers, 3 adenomas) were also analyzed for collagenase-3 mRNA, bu t no expression was detected. In conclusion, our data show that gelatinase A mRNA is expressed in most malignant adrenocortical tumors but not in the benign tumors. Gelatinase A mRNA expression is restricted to stromal cells, whereas its activator, MT1-MMP, is expressed in both stromal and neoplasti c cells. Inhibition of gelatinase A and other proteinases may in the future become important as a form of cancer treatment.