scholarly journals N-WASP coordinates the delivery and F-actin–mediated capture of MT1-MMP at invasive pseudopods

2012 ◽  
Vol 199 (3) ◽  
pp. 527-544 ◽  
Author(s):  
Xinzi Yu ◽  
Tobias Zech ◽  
Laura McDonald ◽  
Esther Garcia Gonzalez ◽  
Ang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Tumor Cells ◽  
Matrix Metalloproteases ◽  
Matrix Remodeling ◽  
Dense Matrix ◽  
Matrix Degradation ◽  
Late Endosomes ◽  
Syndrome Protein

Metastasizing tumor cells use matrix metalloproteases, such as the transmembrane collagenase MT1-MMP, together with actin-based protrusions, to break through extracellular matrix barriers and migrate in dense matrix. Here we show that the actin nucleation–promoting protein N-WASP (Neural Wiskott-Aldrich syndrome protein) is up-regulated in breast cancer, and has a pivotal role in mediating the assembly of elongated pseudopodia that are instrumental in matrix degradation. Although a role for N-WASP in invadopodia was known, we now show how N-WASP regulates invasive protrusion in 3D matrices. In actively invading cells, N-WASP promoted trafficking of MT1-MMP into invasive pseudopodia, primarily from late endosomes, from which it was delivered to the plasma membrane. Upon MT1-MMP’s arrival at the plasma membrane in pseudopodia, N-WASP stabilized MT1-MMP via direct tethering of its cytoplasmic tail to F-actin. Thus, N-WASP is crucial for extension of invasive pseudopods into which MT1-MMP traffics and for providing the correct cytoskeletal framework to couple matrix remodeling with protrusive invasion.

scholarly journals Endosomal WASH and exocyst complexes control exocytosis of MT1-MMP at invadopodia

2013 ◽  
Vol 203 (6) ◽  
pp. 1063-1079 ◽  
Author(s):  
Pedro Monteiro ◽  
Carine Rossé ◽  
Antonio Castro-Castro ◽  
Marie Irondelle ◽  
Emilie Lagoutte ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Carcinoma Cells ◽  
General Mechanism ◽  
Pericellular Matrix ◽  
Matrix Degradation ◽  
Late Endosomes ◽  
The Matrix ◽  
Membrane Type ◽  
Syndrome Protein

Remodeling of the extracellular matrix by carcinoma cells during metastatic dissemination requires formation of actin-based protrusions of the plasma membrane called invadopodia, where the trans-membrane type 1 matrix metalloproteinase (MT1-MMP) accumulates. Here, we describe an interaction between the exocyst complex and the endosomal Arp2/3 activator Wiskott-Aldrich syndrome protein and Scar homolog (WASH) on MT1-MMP–containing late endosomes in invasive breast carcinoma cells. We found that WASH and exocyst are required for matrix degradation by an exocytic mechanism that involves tubular connections between MT1-MMP–positive late endosomes and the plasma membrane in contact with the matrix. This ensures focal delivery of MT1-MMP and supports pericellular matrix degradation and tumor cell invasion into different pathologically relevant matrix environments. Our data suggest a general mechanism used by tumor cells to breach the basement membrane and for invasive migration through fibrous collagen-enriched tissues surrounding the tumor.

scholarly journals Dynamin Participates in Focal Extracellular Matrix Degradation by Invasive Cells

2003 ◽  
Vol 14 (3) ◽  
pp. 1074-1084 ◽  
Author(s):  
Massimiliano Baldassarre ◽  
Arsenio Pompeo ◽  
Galina Beznoussenko ◽  
Claudia Castaldi ◽  
Salvatore Cortellino ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Membrane Surface ◽  
Spatial Relationship ◽  
Matrix Metalloproteases ◽  
Dominant Negative ◽  
Matrix Degradation ◽  
Rich Domain ◽  
Close Spatial Relationship ◽  
Ecm Degradation

The degradation of extracellular matrix (ECM) by matrix metalloproteases is crucial in physiological and pathological cell invasion alike. Degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Herein, we show that the dynamin 2 (Dyn2), a GTPase implicated in the control of actin-driven cytoskeletal remodeling events and membrane transport, is necessary for focalized matrix degradation at invadopodia. Dynamin was inhibited by using two approaches: 1) expression of dominant negative GTPase-impaired or proline-rich domain-deleted Dyn2 mutants; and 2) inhibition of the dynamin regulator calcineurin by cyclosporin A. In both cases, the number and extension of ECM degradation foci were drastically reduced. To understand the site and mechanism of dynamin action, the cellular structures devoted to ECM degradation were analyzed by correlative confocal light-electron microscopy. Invadopodia were found to be organized into a previously undescribed ECM-degradation structure consisting of a large invagination of the ventral plasma membrane surface in close spatial relationship with the Golgi complex. Dyn2 seemed to be concentrated at invadopodia.

scholarly journals Tracking Extracellular Matrix Remodeling in Lungs Induced by Breast Cancer Metastasis. Fourier Transform Infrared Spectroscopic Studies

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 236 ◽  
Author(s):  
Karolina Chrabaszcz ◽  
Katarzyna Kaminska ◽  
Karolina Augustyniak ◽  
Monika Kujdowicz ◽  
Marta Smeda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Fourier Transform ◽  
Cancer Metastasis ◽  
Fourier Transform Infrared ◽  
Muscle Cells ◽  
Breast Cancer Metastasis ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Large Area

This work focused on a detailed assessment of lung tissue affected by metastasis of breast cancer. We used large-area chemical scanning implemented in Fourier transform infrared (FTIR) spectroscopic imaging supported with classical histological and morphological characterization. For the first time, we differentiated and defined biochemical changes due to metastasis observed in the lung parenchyma, atelectasis, fibrous, and muscle cells, as well as bronchi ciliate cells, in a qualitative and semi-quantitative manner based on spectral features. The results suggested that systematic extracellular matrix remodeling with the progress of the metastasis process evoked a decrease in the fraction of the total protein in atelectasis, fibrous, and muscle cells, as well as an increase of fibrillar proteins in the parenchyma. We also detected alterations in the secondary conformations of proteins in parenchyma and atelectasis and changes in the level of hydroxyproline residues and carbohydrate moieties in the parenchyma. The results indicate the usability of FTIR spectroscopy as a tool for the detection of extracellular matrix remodeling, thereby enabling the prediction of pre-metastatic niche formation.

scholarly journals Oriented collagen fibers direct tumor cell intravasation

2016 ◽  
Vol 113 (40) ◽  
pp. 11208-11213 ◽  
Author(s):  
Weijing Han ◽  
Shaohua Chen ◽  
Wei Yuan ◽  
Qihui Fan ◽  
Jianxiang Tian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Fiber Orientation ◽  
Breast Cancer Cells ◽  
Protein Concentration ◽  
Collagen Fiber ◽  
Fiber Alignment ◽  
Local Fiber

In this work, we constructed a Collagen I–Matrigel composite extracellular matrix (ECM). The composite ECM was used to determine the influence of the local collagen fiber orientation on the collective intravasation ability of tumor cells. We found that the local fiber alignment enhanced cell–ECM interactions. Specifically, metastatic MDA-MB-231 breast cancer cells followed the local fiber alignment direction during the intravasation into rigid Matrigel (∼10 mg/mL protein concentration).

scholarly journals Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm

2021 ◽  
Vol 320 (5) ◽  
pp. H1786-H1801
Author(s):  
Brittany O. Aicher ◽  
Jackie Zhang ◽  
Selen C. Muratoglu ◽  
Rebeca Galisteo ◽  
Allison L. Arai ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mouse Model ◽  
Aerobic Exercise ◽  
Thoracic Aortic Aneurysm ◽  
Lysyl Oxidase ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Matrix Degradation ◽  
Aortic Aneurysm And Dissection ◽  
Oxidase Inhibition

Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-β, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise.

scholarly journals New Insights into the Occurrence of Matrix Metalloproteases -2 and -9 in a Cohort of Breast Cancer Patients and Proteomic Correlations

2018 ◽  
Author(s):  
Gianluca Di Cara ◽  
Maria Rita Marabeti ◽  
Rosa Musso ◽  
Ignazio Riili ◽  
Patrizia Cancemi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Basement Membrane ◽  
Cancer Patients ◽  
Family Members ◽  
Extracellular Domain ◽  
Matrix Metalloproteases ◽  
Activity Levels ◽  
Breast Cancer Patients ◽  
Primary Responsibility

Matrix metalloproteases (MMPS) are a family of well-known enzymes which operate prevalently in the extracellular domain, where they fulfil the function of remodeling the extracellular matrix. Within the about 26 family members, encoded by 24 genes in humans, MMP-2 and MMP-9, have been regarded as the primary responsibility for the basement membrane and pericellular ECM rearrangement. In cases of infiltrating carcinomas, which arise from the epithelial tissues of a gland or of an internal organ, a marked alteration of the expression and the activity levels of both MMPs is known to occur. Present investigation represents the continuation and upgrading of our previous studies, now focusing on the occurrence and intensity levels of MMP-2 and -9, and their proteomic correlations, in a cohort of 80 breast cancer surgical tissues

scholarly journals Faciogenital Dysplasia Protein Fgd1 Regulates Invadopodia Biogenesis and Extracellular Matrix Degradation and Is Up-regulated in Prostate and Breast Cancer

2009 ◽  
Vol 69 (3) ◽  
pp. 747-752 ◽  
Author(s):  
Inmaculada Ayala ◽  
Giada Giacchetti ◽  
Giusi Caldieri ◽  
Francesca Attanasio ◽  
Stefania Mariggiò ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation ◽  
Faciogenital Dysplasia

scholarly journals Metalloproteinase MT1-MMP islets act as memory devices for podosome reemergence

2016 ◽  
Vol 213 (1) ◽  
pp. 109-125 ◽  
Author(s):  
Karim El Azzouzi ◽  
Christiane Wiesner ◽  
Stefan Linder
Keyword(s):  
Extracellular Matrix ◽  
Plasma Membrane ◽  
Total Internal Reflection ◽  
Structural Function ◽  
Memory Devices ◽  
Matrix Degradation ◽  
Lytic Enzymes ◽  
Human Macrophages ◽  
Dynamic Cell ◽  
Membrane Bound

Podosomes are dynamic cell adhesions that are also sites of extracellular matrix degradation, through recruitment of matrix-lytic enzymes, particularly of matrix metalloproteinases. Using total internal reflection fluorescence microscopy, we show that the membrane-bound metalloproteinase MT1-MMP is enriched not only at podosomes but also at distinct “islets” embedded in the plasma membrane of primary human macrophages. MT1-MMP islets become apparent upon podosome dissolution and persist beyond podosome lifetime. Importantly, the majority of MT1-MMP islets are reused as sites of podosome reemergence. siRNA-mediated knockdown and recomplementation analyses show that islet formation is based on the cytoplasmic tail of MT1-MMP and its ability to bind the subcortical actin cytoskeleton. Collectively, our data reveal a previously unrecognized phase in the podosome life cycle and identify a structural function of MT1-MMP that is independent of its proteolytic activity. MT1-MMP islets thus act as cellular memory devices that enable efficient and localized reformation of podosomes, ensuring coordinated matrix degradation and invasion.

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