Hallmarks of Cancer: The Next Generation

Cell, Journal Year: 2011, Volume and Issue: 144(5), P. 646 - 674

Published: March 1, 2011

Language: Английский

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Cancer Invasion and the Microenvironment: Plasticity and Reciprocity

Cell, Journal Year: 2011, Volume and Issue: 147(5), P. 992 - 1009

Published: Nov. 1, 2011

Language: Английский

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Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting

FEBS Journal, Journal Year: 2010, Volume and Issue: 278(1), P. 16 - 27

Published: Oct. 21, 2010

Matrix metalloproteinases (MMPs) consist of a multigene family zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays pivotal role tumor growth and the multistep processes invasion metastasis, including proteolytic degradation ECM, alteration cell-cell cell-ECM interactions, migration angiogenesis. The underlying premise current minireview is that MMPs are able to proteolytically process substrates milieu and, so doing, promote progression. However, certain members MMP exert contradicting roles at different stages during cancer progression, depending among other factors on stage, site, enzyme localization substrate profile. therefore amenable therapeutic intervention by synthetic natural inhibitors, providing perspectives for future studies. Multiple agents, called metalloproteinase inhibitors (MMPIs) have been developed target MMPs, attempting control enzymatic activity. Even though clinical trials with these compounds do not show expected results most cases, field MMPIs ongoing. This critically evaluates relation highlights challenges, well prospects, design, development efficacy MMPIs.

Language: Английский

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Physical limits of cell migration: Control by ECM space and nuclear deformation and tuning by proteolysis and traction force

The Journal of Cell Biology, Journal Year: 2013, Volume and Issue: 201(7), P. 1069 - 1084

Published: June 24, 2013

Cell migration through 3D tissue depends on a physicochemical balance between cell deformability and physical constraints. Migration rates are further governed by the capacity to degrade ECM proteolytic enzymes, particularly matrix metalloproteinases (MMPs), integrin- actomyosin-mediated mechanocoupling. Yet, how these parameters cooperate when space is confined remains unclear. Using MMP-degradable collagen lattices or nondegradable substrates of varying porosity, we quantitatively identify limits arrest. MMP-independent declined as linear function pore size with deformation nucleus, arrest reached at 10% nuclear cross section (tumor cells, 7 µm2; T 4 neutrophils, 2 µm2). Residual under restriction strongly depended upon MMP-dependent cleavage enlarging diameters, actomyosin-dependent force generation, which jointly propelled nucleus. The interstitial thus depend scaffold porosity pericellular collagenolysis mechanocoupling modulators.

Language: Английский

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In vitro cell migration and invasion assays

Mutation Research/Reviews in Mutation Research, Journal Year: 2012, Volume and Issue: 752(1), P. 10 - 24

Published: Aug. 23, 2012

Language: Английский

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Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors

Journal of Clinical Investigation, Journal Year: 2012, Volume and Issue: 122(3), P. 899 - 910

Published: Feb. 1, 2012

Appropriate localization and migration of T cells is a prerequisite for antitumor immune surveillance. Studies using fixed tumor samples from human patients have shown that accumulate more efficiently in the stroma than islets, but mechanisms by which this occurs are unknown. By combining immunostaining real-time imaging viable slices lung tumors, we revealed density orientation stromal extracellular matrix likely play key roles controlling cells. Active cell motility, dependent on chemokines not β1 or β2 integrins, was observed loose fibronectin collagen regions, whereas migrated poorly dense areas. Aligned fibers perivascular regions around epithelial dictated migratory trajectory restricted them entering islets. Consistently, reduction with collagenase increased ability to contact cancer Thus, influences immunity positioning Understanding network generated has potential aid development new therapeutics.

Language: Английский

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Chemotaxis in cancer

Nature reviews. Cancer, Journal Year: 2011, Volume and Issue: 11(8), P. 573 - 587

Published: July 22, 2011

Language: Английский

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Dynamic interplay between the collagen scaffold and tumor evolution

Current Opinion in Cell Biology, Journal Year: 2010, Volume and Issue: 22(5), P. 697 - 706

Published: Sept. 7, 2010

Language: Английский

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Actin cortex mechanics and cellular morphogenesis

Trends in Cell Biology, Journal Year: 2012, Volume and Issue: 22(10), P. 536 - 545

Published: Aug. 4, 2012

Language: Английский

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Initial steps of metastasis: Cell invasion and endothelial transmigration

Mutation Research/Reviews in Mutation Research, Journal Year: 2011, Volume and Issue: 728(1-2), P. 23 - 34

Published: May 20, 2011

Metastasis is the leading cause of cancer mortality. The metastatic cascade represents a multi-step process which includes local tumor cell invasion, entry into vasculature followed by exit carcinoma cells from circulation and colonization at distal sites. At earliest stage successful dissemination, primary adapts secondary site involving tumor–stroma crosstalk. migration plasticity as well surrounding environment such stromal endothelial are mandatory. Consequently, mechanisms movement utmost relevance for targeted intervention three different types have been reported. Tumor can migrate either collectively, in mesenchymal or an amoeboid type intravasate blood lymph vasculature. Intravasation interaction with vascular endothelium mechanistically poorly understood. Changes epithelial enable to switch between these motility. may change depending on thereby increasing velocity aggressiveness invading cells. Interference collective invasion targeting integrin expression metalloproteinase activity, respectively, resulted phenotype ultimate strategy There little mechanistic details reported vivo showing that behavior be reversed efficiently inhibited. Future concepts metastasis must simultaneously address collective, order advance anti-metastatic strategies coexist cooperate. Beyond movements, adhesion stroma heterotypic circulating emboli paramount therapy.

Language: Английский

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