Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required  for cell invasion

Nakahara, Hirokazu; Howard, Linda; Thompson, Erik W.; Sato, Hiroshi; Seiki, Motoharu; Yeh, Yunyun; Chen, Wen-Tien

doi:10.1073/pnas.94.15.7959

Cited by 373 publications

(325 citation statements)

References 26 publications

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“…8), strongly suggesting that this type IV collagen-mediated pro-MMP-2 activation might represent a physiologically relevant system. This observation contrasts with the effect of ConA which, despite its high efficiency to promote pro-MMP-2 activation, failed to induce both degradation and invasion of the ECM [61].…”

Section: Type IV Collagen-mediated Mmp-2 Activation Is Associated Witcontrasting

confidence: 72%

“…In this respect, it is interesting to note that even if both TPA and ConA treatments induced the formation of the 62-kDa intermediate MMP-2, only ConA efficiently converted this intermediate into the mature 59-kDa form, as previously reported by Gervasi and coworkers [56]. The ability of ConA to promote the second step of MMP-2 activation (i.e., the intermolecular autolytic cleavage) has been ascribed, at least in part, to its potential to cluster membrane glycoproteins, including MT1-MMP, thereby favoring the autoproteolytic processing of adjacent MT1-MMP-associated intermediate MMP-2 species [56,60,61].…”

Section: Mmp-2 Activation By Tpa-and Cona-treated Ht1080 Cellsmentioning

confidence: 55%

“…As a consequence, the interaction of cell surface anchored MMP-2 with the molecules of type IV collagen is likely to induce the clustering of the MT1-MMP/TIMP-2/MMP-2 ternary complexes at the sites of interaction with the ECM, therefore promoting the intermolecular autocatalytic cleavage required to generate fully mature MMP-2. Alternatively, the transmembrane/cytoplasmic domain of MT1-MMP was previously shown to mediate its localization in invadopodia (specialized membrane extensions present at the sites where invading cells are in close contact with the ECM) where it can interact with several other proteins including integrins [61,70]. Consequently, binding of HT1080 cells to collagen molecules via members of the integrin family could trigger the clustering of invadopodia-associated MT1-MMPs therefore promoting MMP-2 maturation.…”

Section: Mmp-2 Activation By Type Tv Collagen: a Hypothetical Mechanismmentioning

confidence: 99%

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Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Maquoi

Frankenne

Noël

et al. 2000

Experimental Cell Research

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Matrix metalloproteinase 2 (MMP-2) activation has been described as a "master switch" which triggers tumor spread and metastatic progression. We show here that type IV collagen, a major component of basement membranes, promotes MMP-2 activation by HT1080 cells. When plated on plastic, HT1080 cells constitutively processed the 66-kDa pro-MMP-2 into a 62-kDa intermediate activated form, most probably through a membrane type (MT) 1 MMP-dependent mechanism. In the presence of type IV collagen, part of this intermediate form was further processed to fully activated 59-kDa MMP-2. This activation was prevented by tissue inhibitor of MMP (TIMP)-2 and a broad-spectrum hydroxamic acid-based synthetic MMP inhibitor (GI129471). Type IV collagen-mediated pro-MMP-2 activation did not involve either a transcriptional modulation of MMP-2, MT1-MMP, or TIMP-2 expression nor any alteration of MT1-MMP protein synthesis or processing. An inverse relationship between MMP-2 activation and the concentration of secreted TIMP-2 was observed. This is consistent with our previous report that TIMP-2 degradation is probably linked to the MT1-MMP-dependent MMP-2 activation mechanism. Because invasive tumor cells must breach basement membranes at different steps of the metastatic dissemination, the ability of HT1080 cells to activate pro-MMP-2 in the presence of type IV collagen might represent a key regulatory mechanism for the acquisition of an invasive potential.

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Section: Type IV Collagen-mediated Mmp-2 Activation Is Associated Witcontrasting

confidence: 72%

Section: Mmp-2 Activation By Tpa-and Cona-treated Ht1080 Cellsmentioning

confidence: 55%

Section: Mmp-2 Activation By Type Tv Collagen: a Hypothetical Mechanismmentioning

confidence: 99%

See 1 more Smart Citation

Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Maquoi

Frankenne

Noël

et al. 2000

Experimental Cell Research

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“…In tissues from 41 patients with bladder cancer, using nonquantitative RT -PCR, MT1-MMP was shown to associate strongly with decreased survival (Kanayama et al, 1998). Nakahara et al (1997) observed the preferential localisation and functional significance of MT1-MMP in the invadopodia of melanoma cells. Localisation studies suggest that stromally derived MT1-MMP may be cleaved from the cell surface and that the resulting soluble protein is endocytosed and re-expressed by the tumour cells (Chenard et al, 1999), but this is currently unsubstantiated.…”

Section: Discussionmentioning

confidence: 90%

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

et al. 2006

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The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT -PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (Po0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

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“…A complex of TIMP2 and MT1-MMP is now known to be a receptor and activator of MMP2. 3 MMP1, MMP2, MMP3, MMP7, MMP9, MMP11, MMP13, MT1-MMP, TIMP1, and TIMP2 have been detected in various histological types of lung carcinomas. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] However, previous studies rarely examined noninvasive carcinomas, and little is known about how MMP expression differs in noninvasive and invasive carcinomas.…”

mentioning

confidence: 99%

Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components

et al. 2005

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Matrix metalloproteinases (MMPs) are believed to play an essential role in cancer invasion, although detailed differences between noninvasive and invasive lung carcinomas are still unclear. To elucidate the expression and activity patterns of MMPs in noninvasive and invasive carcinoma of the lung, we performed in situ hybridization and real-time reverse transcription-polymerase chain reaction to detect messenger RNAs (mRNAs) of MMPs and their tissue inhibitors (TIMPs). The basement membrane was evaluated by immunohistochemistry for type IV collagen. Gelatinase activity was examined by zymography and in situ zymography. A total of 14 surgically resected primary pulmonary adenocarcinomas were used for this study. All the tumors were adenocarcinoma mixed bronchioloalveolar carcinomas according to the 1999 WHO classification. MMP and TIMP2 mRNAs were detected by in situ hybridization in all samples, in both noninvasive and invasive carcinoma components. Signals for MMP mRNAs were significantly higher in both noninvasive and invasive carcinomas than in tumor-free lung tissue. However, the differences were small between noninvasive and invasive carcinomas, not only in the amount of mRNA but also in the activity of the MMPs. In most carcinomas, stromal fibroblast-type cells tended to express levels of MMP and TIMP2 mRNAs that were higher than or at least similar to those expressed in epithelial cells. Our data on mixed adenocarcinoma suggest that noninvasive carcinoma areas already express a molecular mechanism involving MMPs similar to that expressed by invasive carcinoma areas. Stromal fibroblast-type cells seem to be the most important source of MMPs, from the earliest event of tumor invasion by pulmonary adenocarcinomas. Modern Pathology (2005) 18, 828-837, advance online publication, 14 January 2005; doi:10.1038/modpathol.3800365Keywords: bronchioloalveolar carcinoma; in situ hybridization; matrix metalloproteinase Matrix metalloproteinase (MMP) is essential in remodeling the extracellular matrix. The degradation of the extracellular matrix and basement membranes by MMPs is believed to be crucial in tumor invasion. 1,2 Tissue inhibitor of metalloproteinases (TIMPs) were initially recognized as inhibitors of MMPs, as the name implies. However, subsequent studies revealed that TIMP2 also plays an important role in the activation of MMP2. A complex of TIMP2 and MT1-MMP is now known to be a receptor and activator of MMP2. 3 MMP1, MMP2, MMP3, MMP7, MMP9, MMP11, MMP13, MT1-MMP, TIMP1, and TIMP2 have been detected in various histological types of lung carcinomas. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] However, previous studies rarely examined noninvasive carcinomas, and little is known about how MMP expression differs in noninvasive and invasive carcinomas. Immunohistochemical detection of MMP2 in bronchioloalveolar carcinomas has produced a great variety of results. The expression frequency of MMP2 in bronchioloalveolar carcinomas has been reported to range from 17 to 96%. [19][20][21] This might be du...

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Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion

Abstract: The

Cited by 373 publications

References 26 publications

Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Type IV Collagen Induces Matrix Metalloproteinase 2 Activation in HT1080 Fibrosarcoma Cells

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma

Expression and localization of mRNAs for matrix metalloproteinases and their inhibitors in mixed bronchioloalveolar carcinomas with invasive components

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