Tissue inhibitor of metalloproteinases 1 is an autocrine and paracrine survival factor, with additional immune-regulatory functions, expressed by Hodgkin/Reed-Sternberg cells

Oelmann, Elisabeth; Herbst, Hermann; Zühlsdorf, M.; Albrecht, Oliver; Nolte, A.; Schmitmann, Christiane; Manzke, Oliver; Diehl, Volker; Stein, Harald; Berdel, Wolfgang E.

doi:10.1182/blood.v99.1.258

Cited by 63 publications

(45 citation statements)

References 82 publications

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“…Real-time PCR data showed that the MMP-9/TIMP-1 ratio was noticeably higher in BEL-7402 than in the normal liver cell line L-02 and QSG-7701, TIMP-1 is a multifunctional protein with MMP-dependent and -independent actions for the regulation of cell death, cell proliferation, and angiogenesis (25). After TIMP-1 was initially characterized as a homologue of erythroid potentiating activity factor, it was found to display growth-and survivalpromoting activity for a wide range of normal or transformed cells (26,27). Increasing evidence demonstrates a much more complex role for TIMP-1 during tumor progression and angiogenesis, in addition to its regulation of MMP-mediated ECM degradation.…”

Section: Discussionmentioning

confidence: 99%

TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

Guo¹,

Shen²,

Yang³

et al. 2007

Braz J Med Biol Res

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The tissue inhibitor of metalloproteinases (TIMP)-1 is a multifunctional protein which is not only an inhibitor of matrix metalloproteinases (MMPs) but also to have a possible "cytokine-like" action. Here, we first compared mRNA expression of TIMP-1 and MMP-9 in BEL-7402 (a hepatocellular carcinoma cell line), L-02 (a normal liver cell line) and QSG-7701 (a cell line derived from peripheral tissue of liver carcinoma) using real-time quantitative RT-PCR. By evaluating the variation of the MMP-9/TIMP-1 ratio as an index of reciprocal changes of the expression of the two genes, we observed that the MMP-9/TIMP-1 ratio was about 13-and 5-fold higher in BEL-7402 than in L-02 and QSG-7701, respectively. Significantly, overexpression of TIMP-1 decreased the MMP-9/TIMP-1 ratio in BEL-7402 and then inhibited the cell growth to 60% and reduced the migration to about 30%. Meanwhile, our data showed that interleukin-6 (IL-6) (100 ng/mL) could also inhibited the cell growth of BEL-7402. Further studies indicated that TIMP-1 mediated the inhibitory effect of IL-6 on BEL-7402 cell proliferation in a STAT3-dependent manner, which could further accelerate the expression of the cyclindependent kinase inhibitor p21. A dominant negative STAT3 mutant totally abolished IL-6-induced TIMP-1 expression and its biological functions. The present results demonstrate that TIMP-1 may be one of the mediators that regulate the inhibitory effect of IL-6 on BEL-7402 proliferation in which STAT3 signal transduction and p21 up-regulation also play important roles.

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Section: Discussionmentioning

confidence: 99%

TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

Guo¹,

Shen²,

Yang³

et al. 2007

Braz J Med Biol Res

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“…23,30 Moreover, it has been shown that upregulation of TIMP-1 expression, in a BL cell line, is related to the activation of STAT3. 3 It has been shown that TIMP-1 is expressed in Reed-Sternberg cells of Hodgkin lymphoma 31,32 and subsets of high grade B-cell lymphoma. 4,5 More recently, the existence of a gray zone between diffuse large B-cell lymphoma and Hodgkin lymphoma has been proposed.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

Choi

Lee

et al. 2006

Modern Pathology

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The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To characterize TIMP-1( þ ) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1( þ ) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1( þ ) diffuse large B-cell lymphoma (n ¼ 14) was associated with unfavorable outcomes compared to TIMP-1(À) diffuse large B-cell lymphoma (n ¼ 168) (odds ratio ¼ 2.5, P ¼ 0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein-Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.

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“…In line with this possibility, CD63 has been shown to deliver co-stimulatory signals to T cells 25 and exert an anti-apoptotic effect on other cell types. 26 The interaction between TIMP-1 and haematologica | 2010; 95(11) CD63 may also be involved in the capacity of TIMP-1 to inhibit cell-mediated cytotoxicity, reported by other authors, 27 since CD63 marks the cytolytic granules of cytotoxic cells and its surface expression is increased in active cytotoxic cells. This inhibitory effect may play a role in the development of ALPS and DALD since cellmediated cytotoxicity may partly compensate the apoptosis defect in these diseases.…”

Section: Discussionmentioning

confidence: 99%

Role of tissue inhibitor of metalloproteinases-1 in the development of autoimmune lymphoproliferation

Boggio¹,

Indelicato²,

Orilieri³

et al. 2010

Haematologica

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BackgroundInherited defects decreasing function of the Fas death receptor cause autoimmune lymphoproliferative syndrome and its variant Dianzani's autoimmune lymphoproliferative disease. Analysis of the lymphocyte transcriptome from a patient with this latter condition detected striking over-expression of osteopontin and tissue inhibitor of metalloproteinases-1. Since previous work on osteopontin had detected increased serum levels in these patients, associated with variations of its gene, the aim of this work was to extend the analysis to tissue inhibitor of metalloproteinases-1. Design and MethodsTissue inhibitor of metalloproteinases-1 levels were evaluated in sera and culture supernatants from patients and controls by enzyme-linked immunosorbent assay. Activation-and Fasinduced cell death were induced, in vitro, using anti-CD3 and anti-Fas antibodies, respectively. ResultsTissue inhibitor of metalloproteinases-1 levels were higher in sera from 32 patients (11 with autoimmune lymphoproliferative syndrome and 21 with Dianzani's autoimmune lymphoproliferative disease) than in 50 healthy controls (P<0.0001), unassociated with variations of the tissue inhibitor of metalloproteinases-1 gene. Both groups of patients also had increased serum levels of osteopontin. In vitro experiments showed that osteopontin increased tissue inhibitor of metalloproteinases-1 secretion by peripheral blood monocytes. Moreover, tissue inhibitor of metalloproteinases-1 significantly inhibited both Fas-and activation-induced cell death of lymphocytes. ConclusionsThese data suggest that high osteopontin levels may support high tissue inhibitor of metalloproteinases-1 levels in autoimmune lymphoproliferative syndrome and Dianzani's autoimmune lymphoproliferative disease, and hence worsen the apoptotic defect in these diseases.Key words: osteopontin, tissue inhibitor of metalloproteinases-1, lymphoproliferation, apoptosis, autoimmunity. Haematologica 2010;95(11):1897-1904 doi:10.3324/haematol.2010 This is an open-access paper. Citation: Boggio E, Indelicato M, Orilieri E, Mesturini R, Mazzarino MC, Campagnoli MF, Ramenghi U, Dianzani U, and Chiocchetti A.Role of tissue inhibitor of metalloproteinases-1 in the development of autoimmune lymphoproliferation. Role of tissue inhibitor of metalloproteinases-1 in the development of autoimmune lymphoproliferation

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Tissue inhibitor of metalloproteinases 1 is an autocrine and paracrine survival factor, with additional immune-regulatory functions, expressed by Hodgkin/Reed-Sternberg cells

Cited by 63 publications

References 82 publications

TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

TIMP-1 mediates the inhibitory effect of interleukin-6 on the proliferation of a hepatocarcinoma cell line in a STAT3-dependent manner

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

Role of tissue inhibitor of metalloproteinases-1 in the development of autoimmune lymphoproliferation

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