Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T‐cell lymphomas

Abstract

Degradation of the extracellular matrix by matrix metalloproteinases (MMPs) is a crucial step in tumour invasion and metastasis. In human carcinomas, tumour cell–fibroblast interactions (TFIs) have been demonstrated to play a role in the up‐regulation of MMP levels in tumours, and emmprin is a surface molecule on tumour cells that stimulates nearby fibroblasts to produce MMP‐1, 2, and 3. T‐cell lymphomas frequently show extranodal organ involvement and skin invasion, but a role for TFIs in their invasion has not been examined in detail. This study investigated TFIs in T‐cell lymphomas with special reference to emmprin expression and MMP production. Immunohistochemically, only germinal centre cells and some histiocytes expressed emmprin in non‐neoplastic lymph nodes (ten cases), while all T‐cell lymphomas [14 cases of adult T‐cell leukaemia/lymphoma (ATLL), six cases of lymphoblastic lymphoma, seven cases of anaplastic large cell lymphoma, and nine cases of angio‐immunoblastic T‐cell lymphoma] expressed emmprin strongly and diffusely. FACS analysis of peripheral blood from normal individuals revealed that small fractions of B‐cells, T‐cells, and monocytes expressed emmprin, whereas emmprin‐expressing T‐cells were much increased in number, and expressed this protein to a higher level, in ATLL patients. In vitro co‐cultures of emmprin‐positive HTLV‐1‐transformed lymphocytes (MT‐2) and emmprin‐negative human fibroblasts enhanced the production of pro‐MMP‐2 (gelatinase A) and active MMP‐2, compared with cultures of either cell type alone. This stimulation was inhibited by an activity‐blocking peptide against emmprin. Moreover, in histopathological sections from patients with ATL skin involvement, MMP‐2 was demonstrated in fibroblasts around infiltrating ATL cells, but not in fibroblasts in non‐diseased areas. In conclusion, emmprin is overexpressed by T‐lymphoma cells, when compared with normal counterparts, and facilitates MMP‐2 production via interactions with fibroblasts, which could play a role in stromal invasion by lymphoma cells. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.