Abstract：
:During angiogenesis, anastomosing capillary sprouts align to form complex three-dimensional networks of new blood vessels. Using an endothelial cell spheroid model that was developed to study endothelial cell differentiation processes, we have devised a novel collagen gel-based three-dimensional in vitro angiogenesis assay. In this assay, cell number-defined, gel-embedded endothelial cell spheroids act as a cellular delivery device, which serves as a focal starting point for the sprouting of lumenized capillary-like structures that can be induced to form complex anastomosing networks. Formation of capillary anastomoses is associated with tensional remodeling of the collagen matrix and directional sprouting of outgrowing capillaries towards each other. To analyze whether directional sprouting is dependent on cytokine gradients or on endothelial cell-derived tractional forces transduced through the extracellular matrix, we designed a matrix tension generator that enables the application of defined tensional forces on the extracellular matrix. Using this matrix tension generator, causal evidence is presented that tensional forces on a fibrillar extracellular matrix such as type I collagen, but not fibrin, are sufficient to guide directional outgrowth of endothelial cells. RGD peptides but not control RAD peptides disrupted the integrity of sprouting capillary-like structures and induced detachment of outgrowing endothelial cells cultured on top of collagen gels, but did not inhibit primary outgrowth of endothelial cells. The data establish the endothelial cell spheroid-based three-dimensional angiogenesis technique as a standardized, highly reproducible quantitative assay for in vitro angiogenesis studies and demonstrate that integrin-dependent matrix tensional forces control directional capillary sprouting and network formation.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Korff T,Augustin HGkeywords:
subject
Has Abstractpub_date
1999-10-01 00:00:00pages
3249-58eissn
0021-9533issn
1477-9137journal_volume
112 ( Pt 19)pub_type
杂志文章abstract：:Increased deposition of collagen in extracellular matrix (ECM) leads to increased tissue stiffness and occurs in breast tumors. When present, this increases tumor invasion and metastasis. Precisely how this deposition is regulated and maintained in tumors is unclear. Much has been learnt about mechanical signal transd...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.180539
更新日期：2016-05-15 00:00:00
abstract：:Podosomes, adhesion structures capable of matrix degradation, have been linked with the ability of cells to perform chemotaxis and invade tissues. Wiskott-Aldrich Syndrome protein (WASp), an effector of the RhoGTPase Cdc42 and a Src family kinase substrate, regulates macrophage podosome formation. In this study, we de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.051755
更新日期：2009-11-01 00:00:00
abstract：:Human erythrocytes suspended in buffered isotonic saline were frozen to the temperature of liquid nitrogen at various cooling rates of 3, 140, 700, 1800, 3500, 8000 and 11 500 deg. C/min. The membrane ultrastructure in the frozen state and the extent of haemolysis after thawing were examined at each cooling rate. As t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:Cannabinoid receptors (CBRs) belong to the G protein-coupled receptor superfamily, and activation of CBRs in salivary cells inhibits agonist-stimulated salivation and modifies saliva content. However, the role of different CBR subtypes in acinar cell physiology and in intracellular signalling remains unclear. Here, we...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.088930
更新日期：2012-04-15 00:00:00
abstract：:According to the hypothesis of contact inhibition of movement, cells in a confluent monolayer are restrained from major overlapping by a directional inhibition of locomotion. This explanation of monolayering proposes that contact between 2 cells locally paralyses the locomotory function, preventing movement in the dir...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-04-01 00:00:00
abstract：:The alternative lengthening of telomeres (ALT) mechanism allows cancer cells to escape senescence and apoptosis in the absence of active telomerase. A characteristic feature of this pathway is the assembly of ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs) at telomeres. Here, we dissected the role of...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.148296
更新日期：2015-05-15 00:00:00
abstract：:The sensory functions of cilia are dependent on the enrichment of cilium-resident proteins. Although it is known that ciliary targeting signals (CTSs) specifically target ciliary proteins to cilia, it is still unclear how CTSs facilitate the entry and retention of cilium-resident proteins at the molecular level. We fo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.194019
更新日期：2016-10-15 00:00:00
abstract：:The adaptor protein Miranda plays a pivotal role in the asymmetric cell division of neuroblasts by asymmetrically segregating key differentiation factors. Miranda localization requires Myosin VI and Myosin II. The apical-then-basal localization pattern of Miranda detected in fixed tissue, and the localization defects ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.020024
更新日期：2008-05-01 00:00:00
abstract：:Homophilic binding of E-cadherins through their ectodomains is fundamental to epithelial cell-cell adhesion. Despite this, E-cadherin ectodomains have evolved differently in the vertebrate and insect lineages. Of the five rod-like, tandemly aligned extracellular cadherin domains of vertebrate E-cadherin, the tip extra...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.189258
更新日期：2016-09-01 00:00:00
abstract：:Rab GTPases regulate various membrane trafficking pathways but the mechanisms by which GTPase-activating proteins recognise specific Rabs are not clear. Rab8 is involved in controlling several trafficking processes, including the trafficking of transferrin receptor from the early endosome to the recycling endosome. He...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.102327
更新日期：2012-11-01 00:00:00
abstract：:When a Euglena gracilis in a Ca2+-containing medium is impaled with a microelectrode, the flagellum is instantly ejected. In a Ca2+-free medium to which 1 mM EGTA has been added, the flagellum remains attached to the organism, but it loses activity upon impalement. Externally added ATP at a concentration of 10 mM will...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1977-02-01 00:00:00
abstract：:The post-translational modifications of the G protein of vesicular stomatitis virus, described in the preceding paper, indicate that its transport is arrested by carbonylcyanide m-chlorophenylhydrazone (CCCP) in or near the trans-Golgi. Immunofluorescence microscopy of BHK-21 cells infected with vesicular stomatitis v...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:ARVCF is a novel Armadillo repeat domain protein that is closely related to the catenin p120(ctn). Using new ARVCF monoclonal antibodies, we have found that ARVCF associates with E-cadherin and competes with p120 for interaction with the E-cadherin juxtamembrane domain. ARVCF also localized to the nucleus in some cell...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly undergoing remodeling--i.e. assembly and degradation--particularly during the normal processes of development, differentiati...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.006064
更新日期：2008-02-01 00:00:00
abstract：:Drosophila melanogaster Suppressor of Under-Replication (SuUR) gene encodes a protein that modulates replicative properties of heterochromatin in endocycles of polytene cells. The SuUR mutation abolishes underreplication of intercalary heterochromatin and results in partial underreplication of pericentric heterochroma...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.006007
更新日期：2007-07-15 00:00:00
abstract：:Tenascin, an extracellular matrix protein that modulates cell adhesion, exists as a unique six-armed structure called a hexabrachion. The human hexabrachion is composed of six identical 320 kDa subunits and the structure is stabilized by inter-subunit disulfide bonds between amino-terminal segments. We have examined t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:p63 (also known as TP63) is a transcription factor of the p53 family, along with p73. Multiple isoforms of p63 have been discovered and these have diverse functions encompassing a wide array of cell biology. p63 isoforms are implicated in lineage specification, proliferative potential, differentiation, cell death and ...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.228015
更新日期：2020-09-11 00:00:00
abstract：:Endothelial permeability induced by thrombin and histamine is accompanied by actin stress fibre assembly and intercellular gap formation. Here, we investigate the roles of the Rho family GTPases Rho1, Rac1 and Cdc42 in regulating endothelial barrier function, and correlate this with their effects on F-actin organizati...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:An electron-microscopic study of various fractions taken during a newly developed method for preparation of brush border vesicles from rat duodenum, has shown that vesiculation of microvilli can occur in situ on the brush border membrane. This mode of formation ensures that the vesicle membranes are oriented as in viv...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:Developing oral organelles of dividing Tetrahymena corlissi appear to be positioned by mechanisms which assess distances as a proportion of the organism's overall dimensions. In some respects, the cortex of this protozoan obeys the 'French flag' rule formulated by Wolpert for describing regulation of spatial proportio...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1976-06-01 00:00:00
abstract：:Recently, we demonstrated in cultured endothelial cells and in vivo that deficiency of an isoform of intersectin-1, ITSN-1s, impairs caveolae and clathrin-mediated endocytosis and functionally upregulates compensatory pathways and their morphological carriers (i.e. enlarged endocytic structures, membranous rings or tu...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.163030
更新日期：2015-04-15 00:00:00
abstract：:Coiled bodies are a special type of small round nuclear body, composed of coiled fibers and granules, especially prominent in the nucleoplasm of highly active cells (Brasch and Ochs (1992) Exp. Cell Res. 202, 211-223). Although no specific function has been assigned to coiled bodies, they contain spliceosome snRNAs an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-02-01 00:00:00
abstract：:In plants, many nucleus-encoded proteins are targeted to both mitochondria and plastids, and this process is generally mediated by ambiguous N-terminal targeting sequences that are recognized by receptors on both organelles. In many algae, however, plastids were acquired by secondarily engulfing green or red algae, wh...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.116533
更新日期：2012-12-15 00:00:00
abstract：:Ran is an abundant GTPase of the Ras superfamily that is highly conserved in eukaryotes. In interphase cells, Ran is mainly nuclear and thought to be predominantly GTP-bound, but it is also present in the cytoplasm, probably GDP-bound. This asymmetric distribution plays an important role in directing nucleocytoplasmic...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-07-01 00:00:00
abstract：:Splice variants of certain genes impact on genetic biodiversity in mammals. The tumor suppressor TP53 gene (encoding p53) plays an important role in the regulation of tumorigenesis in hepatocellular carcinoma (HCC). Δ40p53α is a naturally occurring p53 isoform that lacks the N-terminal transactivation domain, yet litt...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.190736
更新日期：2017-02-01 00:00:00
abstract：:The canonical Wnt/β-catenin signaling pathway regulates cell proliferation in development and adult tissue homeostasis. Dysregulated signaling contributes to human diseases, in particular cancer. Growing evidence suggests a role for clathrin and/or endocytosis in the regulation of this pathway, but conflicting results...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.244467
更新日期：2020-07-09 00:00:00
abstract：:The beta 2-tubulin isotype of Physarum polycephalum is only 83% identical in amino acid sequence with the constitutively expressed beta 1B-tubulin and the myxamoeba-specific beta 1A-tubulin isotypes. A polyclonal antibody specific for beta 2-tubulin was used to monitor the subcellular distribution of the beta 2-tubuli...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:We have discovered a novel mitosis-specific human autoantigen that arises at the centromeres of prophase chromosomes, but ultimately participates in formation of an organelle that bisects the cell at late anaphase and during telophase. The organelle, discernible as a three-dimensional disc by confocal microscopy, enco...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:Excitatory amino acid transporter type 3 (EAAT3, also known as SLC1A1) is a high-affinity, Na(+)-dependent glutamate carrier that localizes primarily within the cell and at the apical plasma membrane. Although previous studies have reported proteins and sequence regions involved in EAAT3 trafficking, the detailed mole...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.185496
更新日期：2016-08-15 00:00:00
abstract：:Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for no...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.240077
更新日期：2020-05-14 00:00:00
