Tumorigenic potential of extracellular matrix metalloproteinase inducer

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein pr esent on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibrob lasts synthesize most of the MMPs in human tumors rather than the cancer ce lls themselves has ignited interest in the role of EMMPRIN in tumor dissemi nation. In this report we have demonstrated a role for EMMPRIN in cancer pr ogression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected ortho topically into mammary tissue of female NCr nu/nu mice. Green fluorescent p rotein was used to visualize metastases. In three experiments, breast cance r cell clones transfected with EMMPRIN cDNA were considerably more tumorige nic and invasive than plasmid-transfected cancer cells. Increased gelatinas e A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors, In contrast to ne novo breast canters in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.