Emmprin, a cell surface inducer of matrix metalloproteinases (MMPs), is expressed in T-cell lymphomas.
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.
Department of Pathology, Fukuoka University School of Medicine, Fukuoka, Japan.
Kazuki
K
Nabeshima
Junji
J
Suzumiya
Mitsuyuki
M
Nagano
Koichi
K
Ohshima
Bryan P
BP
Toole
Kazuo
K
Tamura
Hiroshi
H
Iwasaki
Masahiro
M
Kikuchi
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D051926:Basigin; D015415:Biomarkers / Q000032:analysis; D045744:Cell Line, Tumor; D002648:Child; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008198:Lymph Nodes / Q000201:enzymology; D016399:Lymphoma, T-Cell / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C497886:BSG protein, human; D015415:Biomarkers; D008562:Membrane Glycoproteins; D051926:Basigin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2