Expression of EMMPRIN by oral squamous cell carcinoma

A transmembrane glycoprotein recently identified on some tumor cells, extra cellular matrix metalloproteinase inducer (EMMPRIN), has been shown to indu ce metalloproteinase (MMP) production by peritumor fibroblasts (PTF). We ex amined biopsy specimens of normal human oral mucosa and oral squamous cell carcinoma (SCC) for expression of EMMPRIN. In normal mucosa, EMMPRIN was ex pressed at the cell membrane throughout the epithelium with a slight enhanc ement along the basal cell layer. In oral SCC, EMMPRIN was expressed at the cell membrane throughout the entire lesion. Immunofluorescence microscopy localized EMMPRIN to the cell membrane in a highly invasive oral SCC cell l ine in agreement with our in vivo observations. Function-blocking antibodie s to EMMPRIN significantly inhibited oral SCC cell migration on tenascin-C (TN-C) and fibronectin as well as invasion through a reconstituted basement membrane (RBM). We previously showed that soluble factors from SCC cells a nd PTF are required for deposition of a TN-C matrix. To determine whether E MMPRIN may modulate the release or expression of these soluble factors, we again used function-blocking antibodies. Antibodies to EMMPRIN completely i nhibited the organization of TN-C matrices and partially reduced the deposi tion of FN matrices by oral SCC cell /PTF co-cultures. In addition, antibod ies to EMMPRIN perturbed the expression of MMP-2. Moreover, antibodies to M MP-2 perturbed oral SCC cell invasion of an RBM by approx. 75%. Our results demonstrate that EMMPRIN is highly expressed in oral SCC, facilitates tumo r cell motility, and mediates TN-C matrix deposition. Taken together, these results suggest that EMMPRIN may help regulate oral squamous cell carcinom a invasion. (C) 2000 Wiley-Liss.