Control of matrix metalloproteinase catalytic activity

Ra, Hyun-Jeong; Parks, William C.

doi:10.1016/j.matbio.2007.07.001

Cited by 540 publications

(545 citation statements)

References 102 publications

(98 reference statements)

Supporting

Mentioning

474

Contrasting

Unclassified

Order By: Relevance

“…MMP modulation is also closely linked to bone remodeling (39,40). In this regard, a study using a canine model of experimental OA showed that during the disease, some members of the MMP family are selectively located at the active subchondral bone resorption zone (19).…”

Section: Discussionmentioning

confidence: 99%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Abnormal subchondral bone metabolism is involved in osteoarthritis (OA). It has been suggested that ephrin B2 and its specific receptor EphB4 participate in bone homeostasis. We previously reported that human OA subchondral bone osteoblasts could be classified into 2 subpopulations: low (L), having proresorption properties, and high (H), having proformation properties. The purpose of this study was to investigate the importance of the ephrin system in OA subchondral bone osteoblasts.Methods. The presence of the EphB4 receptor was determined by immunohistochemistry, and its expression level, modulation upon treatment, and consequences of activation by ephrin B2 were determined by quantitative polymerase chain reaction. The effects of ephrin B2 activation of the EphB4 receptor on bone resorption activity were also determined. EphB4 receptor activation signaling pathways were investigated by specific enzyme-linked immunosorbent assay.Results. EphB4 receptors were present in subchondral bone osteoblasts and osteocytes. Compared with normal and H-OA osteoblasts, EphB4 receptor expression levels were significantly increased in L-OA osteoblasts, with no difference between normal and H-OA osteoblasts. EphB4 receptor levels in L-OA osteoblasts were significantly up-regulated by prostaglandin E 2 (PGE 2 ) and interleukin-17 (IL-17). Ephrin B2, PGE 2 , and IL-17 significantly inhibited bone resorption activity in these cells. EphB4 activation by ephrin B2 significantly inhibited the expression of IL-1␤, IL-6, matrix metalloproteinase 1 (MMP-1), MMP-9, MMP-13, and RANKL, but not MMP-2 and osteoprotegerin. EphB4 receptor activation significantly inhibited the phosphatidylinositol 3-kinase/Akt pathway.Conclusion. This study is the first to provide evidence that EphB4 receptor activation by ephrin B2 in OA subchondral bone could affect abnormal metabolism in this tissue by inhibiting resorption factors and their activities. Ephrin B2 could be targeted as a specific therapeutic approach in the development of a diseasemodifying OA drug.Subchondral bone is made up of a specialized connective tissue formed by a mineralized matrix containing the specific type I collagen, proteoglycans, and several growth factors and cytokines, as well as bonespecific cell types (osteoblasts, osteocytes, and osteoclasts) (1,2). Osteoblast and osteoclast activities, either alone or in combination, contribute to the bone remodeling process, and any disturbance in the activities of these 2 cells is responsible for the development of altered bone metabolism.The ephrin B molecules (ephrin B1, ephrin B2, and ephrin B3) bind in a specific manner to their EphB

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Tat¹,

Pelletier²,

Amiable³

et al. 2008

Arthritis & Rheumatism

View full text Add to dashboard Cite

show abstract

“…Interestingly, treatment of B16F10 cells with S100A8/S100A9 also stimulated the expression of furin (Fig. 6, A and B), a pro-protein convertase that regulates the enzymatic activity of some MMPs such as MMP-14 (MT1-MMP) (44). Thus, it is likely that furin activated MMP-14, which in turn activated MMP-2.…”

Section: Elevated Levels Of Metastasis In the Lungs Of Mice Lacking Umentioning

confidence: 91%

“…Thus, it is likely that furin activated MMP-14, which in turn activated MMP-2. This notion is supported by the demonstration that heterodimerization of activated MMP-14 with MMP-2 activates MMP-2 (44). The mechanism of activation of MMP-9 remains unclear.…”

Section: Elevated Levels Of Metastasis In the Lungs Of Mice Lacking Umentioning

confidence: 95%

Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs

Saha

Lee

Zhang

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Emerging evidence indicates a link between inflammation and cancer metastasis, but the molecular mechanism(s) remains unclear. Uteroglobin (UG), a potent anti-inflammatory protein, is constitutively expressed in the lungs of virtually all mammals. UG-knock-out (UG-KO) mice, which are susceptible to pulmonary inflammation, and B16F10 melanoma cells, which preferentially metastasize to the lungs, provide the components of a model system to determine how inflammation and metastasis are linked. We report here that B16F10 cells, injected into the tail vein of UG-KO mice, form markedly elevated numbers of tumor colonies in the lungs compared with their wild type littermates. Remarkably, UG-KO mouse lungs overexpress two calcium-binding proteins, S100A8 and S100A9, whereas B16F10 cells express the receptor for advanced glycation end products (RAGE), which is a known receptor for these proteins. Moreover, S100A8 and S100A9 are potent chemoattractants for RAGE-expressing B16F10 cells, and pretreatment of these cells with a blocking antibody to RAGE suppressed migration and invasion. Interestingly, in UG-KO mice S100A8/S100A9 concentrations in blood are lowest in tail vein and highest in the lungs, which most likely guide B16F10 cells to migrate to the lungs. Further, B16F10 cells treated with S100A8 or S100A9 overexpress matrix metalloproteinases, which are known to promote tumor invasion. Most notably, the metastasized B16F10 cells in UG-KO mouse lungs express MMP-2, MMP-9, and MMP-14 as well as furin, a pro-protein convertase that activates MMPs. Taken together, our results suggest that a lack of an anti-inflammatory protein leads to increased pulmonary colonization of melanoma cells and identify RAGE as a potential anti-metastatic drug target.It is estimated that more than 90% of human cancer deaths result from metastasis (1-8), a complex process in which the cells from a primary tumor successfully invade and colonize a distant organ (6 -9). It has long been suspected that a functional relationship exists between inflammation and cancer. Indeed, in 1863, Virchow observed that cancer develops at locations where chronic inflammation is present. This hypothesis is partly based on his assumption that some substances that cause tissue injury and inflammation also enhance cell proliferation (10). Although it is clear now that proliferation alone does not account for cancer, the cause and effect relationship between inflammation and cancer is widely accepted. Nonetheless, many aspects of the molecular and cellular mechanisms that link inflammation, migration, and establishment of tumor colonies in a distant organ remain unresolved (5). Recently, it has been reported that a tumor microenvironment actively contributes to cancer initiation, progression, and metastasis (11, 12). It has also been suggested that reductions in the rates of cancer morbidity and mortality may be achieved by gaining greater understanding of the molecular mechanism(s) of tumor cell migration, invasion, and establishment of colonies (13). In this regard...

show abstract

“…10 The glutamate residue at the zinc binding motif activates the zinc-bound water molecule to provide the nucleophile during cleaving activities on peptide bonds. 11 A mutation in the zinc-binding motif from glutamate (E) to alanine (A) causes a loss of MMP19 function in cell proliferation, migration, and protein degradation in a human keratinocyte cell model. 12 MMP19 was first isolated as an autoantigen from the synovium of a rheumatoid arthritis patient.…”

mentioning

confidence: 99%

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Chan

Lung

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

The association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC.Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelial cells of the nasopharynx. This cancer has a unique racial and geographic distribution with a high incidence in Southern China and Southeast Asia among the Southern Chinese population. 1 The etiology of NPC is believed to be multifactorial including dietary and

show abstract

Control of matrix metalloproteinase catalytic activity

Cited by 540 publications

References 102 publications

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts

Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Contact Info

Product

Resources

About