LOCALIZATION OF MESSENGER-RNA FOR TISSUE INHIBITOR OF METALLOPROTEINASES-1 AND TYPE-IV COLLAGENASES GELATINASES IN MONKEY HEPATOCELLULAR CARCINOMAS/

Studies of tissue inhibitors of metalloproteinases (TIMPs) suggest tha t one of their main functions is to inhibit metalloproteinase (MMP) ac tivity and thus prevent tumor invasion by preserving extracellular mat rix (ECM) integrity. In the present study we examined the distribution of transcripts for TIMP-1, MMP-2 and MMP-9 in monkey hepatocellular c arcinoma tissues. In situ hybridization demonstrated elevated levels o f TIMP-1 transcripts in fibrous tissue septa, tumor inflammatory infil trate, tumor blood vessels and in expanded portal areas. However, elev ated transcripts for MMP-2 and MMP-9 were found only in tumor inflamma tory infiltrate. In lung metastasis high levels of TIMP-1 transcripts were found in the stromal cells surrounding necrotic tumor nodules, in tumor blood vessels, and in mesothelial cells, MMP-9 transcripts were elevated at the periphery of the necrotic tumor nodules. These findin gs suggest that TIMP-1 and type IV collagenases/gelatinases can be ind ependently regulated in vivo and that TIMP-1 may have functions in ECM remodeling which are unrelated to inhibition of MMP activity.