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.

HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma

“…CD147 expression is elevated on several human tumors and has been correlated with the malignancy in some cancers such as primary breast cancer and ovarian cancer, etc. (7)(8)(9)(10)(11)(12). Despite the close correlation between CD147 expression and malignancy of some tumors, it is not clear whether CD147 has a functional role in tumor genesis and hepatocellular carcinoma (HCC) progression.…”

Synthetic emmprin peptides inhibit tumor cell-fibroblast interaction-stimulated upregulation of MMP-2 and tumor cell invasion

“…In situ hybridization studies of human surgical specimens have shown that stromal fibroblasts are the predominant source of MMP-2 in most carcinomas (2)(3)(4). Carcinoma cells stimulate nearby fibroblasts to produce MMPs via soluble cytokines and growth factors, or by cell surface interactions mediated by plasma membrane proteins, such as emmprin (5)(6)(7). Emmprin, also called basigin/CD147, is expressed in significantly higher levels in tumor cells than in normal cells.…”

Tumor-enhancing activity of Basigin expression in gallbladder carcinoma and its prognostic role

“…Basigin, also known as extracelluar matrix metalloproteinase inducer (EMMPRIN/CD147), is a highly glycosylated member of the immunoglobulin superfamily that is expressed on the surface of many malignant tumor cells and functions as an upstream modulator of matrix metalloproteinase (MMP) production in the local tumor environment (6)(7)(8). Recently, it was demonstrated that Basigin may bind and regulate several tumor-related signalling proteins and stimulate cell proliferation and survival (9).…”