Matrix metalloproteinase-14 induces epithelial-to-mesenchymal transition in synovial sarcoma

Liu, Manli; Yan, Qi; Zhao, Lili; Chen, Dongdong; Zhou, Yang; Zhou, Hongrun; Lv, Yanmin; Zhang, Lu; Jin, Shan; Li, Shugang; Zou, Hong; Jia, Wei Hua; Wang, Cuicui; Jiang, Jinfang; Liang, Wei; Pang, Lijuan; Li, Feng

doi:10.1016/j.humpath.2017.12.031

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…While MMP-19 is a pure mesenchymal marker like the proteoglycan asporin, other MMPs are also significantly involved in EMT [ 31 , 33 , 34 ]. MMPs with a demonstrated role in the EMT are MMPs -1, -2, -3, -7, -9, -14, and -28 [ 17 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ] ( Table 1 ). MMP-14 induces a mesenchymal phenotype in cancer and development, by cleaving BM components as well as E-cadherin [ 42 , 43 , 44 , 45 , 46 ].…”

Section: Cancer Progression Is Driven By Mmps In the Tmementioning

confidence: 99%

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Niland

Riscanevo

Eble

2021

IJMS

189

107

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Cancer progression with uncontrolled tumor growth, local invasion, and metastasis depends largely on the proteolytic activity of numerous matrix metalloproteinases (MMPs), which affect tissue integrity, immune cell recruitment, and tissue turnover by degrading extracellular matrix (ECM) components and by releasing matrikines, cell surface-bound cytokines, growth factors, or their receptors. Among the MMPs, MMP-14 is the driving force behind extracellular matrix and tissue destruction during cancer invasion and metastasis. MMP-14 also influences both intercellular as well as cell–matrix communication by regulating the activity of many plasma membrane-anchored and extracellular proteins. Cancer cells and other cells of the tumor stroma, embedded in a common extracellular matrix, interact with their matrix by means of various adhesive structures, of which particularly invadopodia are capable to remodel the matrix through spatially and temporally finely tuned proteolysis. As a deeper understanding of the underlying functional mechanisms is beneficial for the development of new prognostic and predictive markers and for targeted therapies, this review examined the current knowledge of the interplay of the various MMPs in the cancer context on the protein, subcellular, and cellular level with a focus on MMP14.

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Section: Cancer Progression Is Driven By Mmps In the Tmementioning

confidence: 99%

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Niland

Riscanevo

Eble

2021

IJMS

189

107

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“…68 It could also represent cells undergoing EMT prior to moving into the blood vessels as reported in other sarcomas, 70 with MT1-MMP already being identified as a driver of this process in both embryogenesis 29 and cancer. [30][31][32][33] Although the high-expressing, perivascular cells appear Ewing-like in their morphology, without co-localisation studies and staining for CD99, it is impossible to confirm this, although the fact they were stained for CD99 during the diagnostic process is reassuring. Additionally, staining for vascular markers, such as CD31, is required to confirm that the vascular-like structures are actually blood vessels.…”

Section: Discussionmentioning

confidence: 99%

“…21 These properties are consistent with the role of MT1-MMP in invasion and migration [22][23][24][25][26][27] and development of metastasis in vivo. 24,28 The ability of MT1-MMP to regulate epithelial-to-mesenchymal transition (EMT) during development 29 is also hijacked in multiple cancers including synovial sarcoma, [30][31][32][33] in which adopting an invasive, mesenchymal phenotype aides metastasis. 34 Furthermore, knockdown of caveolin-1, the protein regulating the expression of MT1-MMP at the cell surface, reduces ES metastasis in mouse models, 35 while the inactivation of ICAM-1 inhibits metastasis and improves outcome in ES.…”

Section: Introductionmentioning

confidence: 99%

Membrane‐type 1 matrix metalloproteinase as predictor of survival and candidate therapeutic target in Ewing sarcoma

Brookes

Roundhill

Jeys

et al. 2022

Pediatric Blood & Cancer

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Background: Ewing sarcoma (ES) is the second most common primary bone malignancy, with an urgent need for new treatments. ES is associated with high rates of progression and relapse, driven by drug-resistant cells capable of migration, self-renewal and single-cell tumorigenesis, termed cancer stem-like cells (CSCs). Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a membrane-bound proteolytic enzyme, which, via direct and indirect mechanisms, digests four of the main types of collagen.This can be hijacked in malignancy for invasion and metastasis, with high expression predicting decreased survival in multiple cancers. In this study, we have examined the hypothesis that MT1-MMP is expressed by ES cells and explored the relationship between expression and outcomes.Procedure: MT1-MMP expression in ES established cell lines, primary patient-derived cultures and daughter ES-CSCs was characterised by RNA sequencing, Western blotting, immunocytochemistry and flow cytometry. Immunohistochemistry was used to detect MT1-MMP in tumour biopsies, and the relationship between expression, event-free and overall survival examined.Results: MT1-MMP was detected at both RNA and protein levels in five of six established cell lines, all primary cultures (n = 25) and all daughter ES-CSCs (n = 7).Immunohistochemistry of treatment-naïve biopsy tissue demonstrated that high MT1-MMP expression predicted decreased event-free and overall survival (p = .017 and .036, respectively; n = 47); this was not significant in multivariate analysis. Conclusions: MT1-MMP is expressed by ES cells, including ES-CSCs, making it a candidate therapeutic target. The level of MT1-MMP expression at diagnosis may be considered as a prognostic biomarker if validated by retrospective analysis of a larger cohort of clinical trial samples.

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“…Moreover, transcriptomic data from the Cancer Genome Atlas program (TCGA) shows a significant correlation between the expression of MMP14 and the transcription factors TWIST ( TWIST1 : r = 0.4, p = 8.31 × 10 −11 ; TWIST2 : r = 0.21, p = 9.72 × 10 −4 ) and SNAI ( SNAI1 : Pearson’s r = 0.23, p = 3.08 × 10 −4 ; SNAI2 : r = 0.21, p = 9.96 × 10 −4 ) in sarcomas, suggesting that MMP14 expression is coupled with the transcriptional program governing the sarcoma phenotype. Experimentally, MMP14 overexpression in the synovial sarcoma cell line SW982 has been shown to induce spindle shape morphology and an EMT-like phenotype, in conjunction with enhanced cell invasiveness [65]. Together, these reports establish the tight association between MMP14 and the mesenchymal phenotype, suggesting that MMP14 may also contribute to determining the phenotypical characteristics of sarcomas.…”

Section: Mmp14 and The Mesenchymal Phenotypementioning

confidence: 95%

“…In synovial sarcoma, MMP14 protein expression is higher in TNM stages III and IV than in stages I and II, and the expression of MMP14 correlates with that of EMT-related proteins such as increased N-cadherin and decreased E-cadherin. Moreover, high MMP14 expression is mainly observed in spindle cell monophasic fibrous synovial sarcomas [65]. In synovial sarcoma and liposarcoma, enhanced MMP2 protein also correlates with poor disease-free survival and in liposarcoma it correlates with both tumor grade and metastasis [70].…”

Section: Mmp14 In Sarcomamentioning

confidence: 99%

MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues

Gonzalez‐Molina

Gramolelli

Liao

et al. 2019

Cells

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Sarcomas are deadly malignant tumors of mesenchymal origin occurring at all ages. The expression and function of the membrane-type matrix metalloproteinase MMP14 is closely related to the mesenchymal cell phenotype, and it is highly expressed in most sarcomas. MMP14 regulates the activity of multiple extracellular and plasma membrane proteins, influencing cell–cell and cell–extracellular matrix (ECM) communication. This regulation mediates processes such as ECM degradation and remodeling, cell invasion, and cancer metastasis. Thus, a comprehensive understanding of the biology of MMP14 in sarcomas will shed light on the mechanisms controlling the key processes in these diseases. Here, we provide an overview of the function and regulation of MMP14 and we discuss their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas.

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Matrix metalloproteinase-14 induces epithelial-to-mesenchymal transition in synovial sarcoma

Cited by 11 publications

References 26 publications

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

Membrane‐type 1 matrix metalloproteinase as predictor of survival and candidate therapeutic target in Ewing sarcoma

MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues

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