Soluble EMMPRIN (extra-cellular matrix metalloproteinase inducer) stimulates the migration of HEp-2 human laryngeal carcinoma cells, accompanied by increased MMP-2 production in fibroblasts

The basement membrane functions as a barrier against the invasion of cancer cells. It is therefore important to investigate the mechanism of basement membrane degradation by matrix metalloproteinases (MMPs). Previously, cancer cells were long considered to be the major source of MMPs; however, current evidence indicates that most MMPs in cancer tissue are produced by stromal rather than cancer cells. A glycoprotein highly expressed on the cancer-cell membrane, EMMPRIN (extra-cellular matrix metalloproteinase inducer), exhibits the potential role of the MMP inductor in stromal cells. Depending on the cell type, EMMPRIN can stimulate the production of MMP-1, MMP-2, and MMP-3. We here report that soluble full-length EMMPRIN is liberated from HEp-2 human laryngeal epidermoid carcinoma cells, probably via microvesicle shedding. Soluble EMMPRIN stimulates human fibroblasts to produce MMP-2, after which the augmented migration of HEp-2 cells occurs, as observed in an invasion chamber assay with separately cultured fibroblasts. An anti-EMMPRIN function-blocking antibody reduced MMP-2 activity in the conditioned medium and inhibited the migration of HEp-2; obviously, EMMPRIN activity contributes to cancer-cell migration. We postulate that soluble EMMPRIN probably triggers the promotion of cancer invasion in vivo.