Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells

Alla, Vijay; Kashyap, Anubha; Gregor, Sebastian; Theobald, Matthias; Heid, Hans; Galle, Peter R.; Strand, Dennis; Strand, Susanne

doi:10.1016/j.canlet.2008.04.006

Cited by 5 publications

(5 citation statements)

References 37 publications

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“…However, this could have been the result of differences between cancer cells and lymphocytes or the expression intensity of MMP-7. In addition, Alla et al reported that the human leukocyte elastase secreted by polymorphonuclear leukocytes could act as a natural inactivator of MMP-7 (51), indicating that MMP-7 expressed on lymphocytes might be inactivated steadily by leukocyte elastase. Like MMP-7, constitutively expressed ADAM-10 did not participate in sRANKL cleavage from activated PBLs, contrary to Hikita’s report (12) showing that shedding of mRANKL expressed on osteoblasts by ADAM10 and MMP14 down-regulates osteoclastogenesis in the in vitro co-culture of osteoblasts and bone marrow macrophages.…”

Section: Discussionmentioning

confidence: 99%

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

Kanzaki

Makihira

Suzuki

et al. 2016

The Journal of Immunology

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Host immune responses play a key role in promoting bone resorption in periodontitis via RANKL-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear. Tumor necrosis factor-α-converting enzyme (TACE) is reported to cleave 1) precursor TNF-α with release of mature, soluble TNF-α (sTNF-α) and 2) mRANKL with release of sRANKL. Both sTNF-α and sRANKL are found in the periodontitis lesion, leading to the hypothesis that TACE expressed on lymphocytes is engaged in RANKL shedding and that the resulting sRANKL induces osteoclastogenesis. In the present study, upon stimulating peripheral blood lymphocytes (PBLs) with mitogens in vitro, RANKL expression, sRANKL secretion, and TACE expression were all upregulated. Among the four putative mRANKL sheddases examined in neutralization assays, TACE was the only functional sheddase able to cleave mRANKL expressed on PBL. Moreover, PBL culture supernatant stimulated with mitogens in the presence of anti-TACE-antibody or anti-RANKL-antibody showed a marked reduction of osteoclastogenesis from osteoclast precursors, indicating that TACE-mediated sRANKL may possess sufficient osteoclastogenic activity. According to double-color confocal microscopy, B cells expressed a more pronounced level of RANKL and TACE expression than T cells or monocytes in periodontally diseased gingiva. Conditioned medium of patients’ gingival lymphocyte culture increased in vitro osteoclastogenic activity, which was suppressed by the addition of anti-TACE-antibody and anti-RANKL-antibody. Therefore, TACE-mediated cleavage of sRANKL from activated lymphocytes, especially B cells, can promote osteoclastogenesis in periodontitis.

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Section: Discussionmentioning

confidence: 99%

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

Kanzaki

Makihira

Suzuki

et al. 2016

The Journal of Immunology

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“…Mitsiades et al (37) demonstrated one mechanism whereby MMP-7 promotes tumor survival rate and resistance to doxorubicin through cleavage of FasL. Proteolysis of the ligand was found to reduce its effectiveness in triggering Fas-mediated apoptosis (41). Insulin-like growth factor-1 (IGF-I) bioavailability has been demonstrated to be regulated by MMP-7 proteolysis of IGFBP-3, leading to the promotion of cell survival (42).…”

Section: Discussionmentioning

confidence: 99%

Effect of fractionated irradiation on the expression of multidrug resistance genes in the CNE1 human nasopharyngeal carcinoma cell line

Yang

Sui

et al. 2012

Molecular Medicine Reports

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Nasopharyngeal carcinoma (NPC) often develops drug resistance following radiotherapy. The molecular basis of radiotherapy-related multidrug resistance (MDR) remains unclear. In the present study, we investigated the effect of fractionated irradiation on the expression of the MDR-1 gene and the MDR-associated protein P-glycoprotein (P-gp) in CNE1 human NPC cells. CNE1 cells were treated with fractionated X-rays. Drug resistance was determined by MTT assay. The expression levels of MDR-1 and P-gp were analyzed by RT-PCR and western blot analysis, respectively. Differential expression was analyzed by gene chips. The results revealed that low levels of mRNA expression of MDR1 were present in non-irradiated CNE1 cells. Compared with the control, the expression of MDR1 mRNA was gradually increased following fractionated irradiation. On day 21, the expression of MDR1 mRNA was increased 1.59- and 2.19-fold, compared with the control, by treatment with 10 and 20 Gy, respectively. We observed decreased MDR1 expression following treatment with 10 and 20 Gy irradiation on days 28 and 35, compared with day 21. On days 21, 28 and 35, expression was increased 1.37-, 1.40- and 1.15-fold by treatment with 20 Gy compared with 10 Gy. Expression of MDR1 was significantly upregulated by treatment with 50 Gy irradiation compared with the control on days 78 and 106. P-gp expression was consistent with that of MDR1 mRNA expression. The sensitivity of CNE1 cells to cisplatin was reduced following irradiation compared with the control. A total of 26 genes were significantly upregulated and 8 genes were significantly downregulated compared with the control. Results of the present study have shown that MDR1 and P-gp are upregulated in CNE1 cells following irradiation. Multiple genes were involved in the mechanism of radiation-induced drug resistance.

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“…MMPs mayalsoindirectlyactivategrowthfactorsthroughtheinactivation of their negative regulators or by proteolysis of their transporters.Forexample,MMP-1,-2,and-3allmaycleave insulin-likegrowthfactor-bindingprotein-3(IGFBP-3)which acts as a main transporter of insulin-like growth factor-1 (IGF-1)andakeymodulatorofIGF-1signaling [32].Finally, MMP activity may alter other signaling proteins. MMPs can also regulate tumor growth by promoting or inhibiting apoptosis [33].…”

Section: Membrane-type Mmpsmentioning

confidence: 99%

Matrix Metalloproteinases and Their Role in Oncogenesis: A Review

Pytliak¹,

Vargová²,

Mechírová

2012

Onkologie

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The extracellular matrix (ECM) provides a physical framework for the cells and functions as a gel medium. Remodeling of the ECM is crucial during physiological cell migration, proliferation, growth, and development. Thus, the interaction between cells and the ECM plays a key role in normal development and differentiation of organisms. However, remodeling of the ECM also occurs in many pathological states. Changes in the ECM are regulated by a system of proteolytic enzymes that are responsible for the proteolysis of a huge quantity of ECM components. Matrix metalloproteinases (MMPs) represent the main group of regulating proteases in the ECM. By regulating the composition and integrity of the ECM, this group of enzymes is essential for cell proliferation, differentiation, and processes of apoptosis. However, deregulation or activation of MMP expression is a feature of numerous pathologic conditions including tumorigenesis and metastasis. The aim of this article is to provide a brief overview of MMPs, their nomenclature and structure, and their role in the development of tumors and metastases.

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Human leukocyte elastase counteracts matrix metalloproteinase-7 induced apoptosis resistance of tumor cells

Cited by 5 publications

References 37 publications

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

Soluble RANKL Cleaved from Activated Lymphocytes by TNF-α–Converting Enzyme Contributes to Osteoclastogenesis in Periodontitis

Effect of fractionated irradiation on the expression of multidrug resistance genes in the CNE1 human nasopharyngeal carcinoma cell line

Matrix Metalloproteinases and Their Role in Oncogenesis: A Review

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