Crossing the endothelial barrier during metastasis

Reymond, Nicolas; d’Água, Bárbara Borda; Ridley, Anne J.

doi:10.1038/nrc3628

Cited by 734 publications

(764 citation statements)

References 144 publications

Supporting

Mentioning

743

Contrasting

Unclassified

Order By: Relevance

“…Recruitment of various circulating blood cells such as macrophages, neutrophils or platelets by tumour-derived factors has been recognized to assist tumour cell extravasation at metastatic sites 8,49 . In this regard, CCL2 that we identified in our proteomic analysis, was recently shown to attract myeloidderived monocytes and to promote efficient colon cancer cell extravasation 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Physiological and pathological pathways that increase endothelial permeability act through disruption of intercellular junctions and acto-myosin contractibility 8 . A survey of signalling pathways activated by SPARC-competent melanoma CM on endothelial cells identified the p38 MAPK pathway as responsible for tumour-induced actin cytoskeleton remodelling and intercellular pores formation.…”

Section: Discussionmentioning

confidence: 99%

“…The opening of endothelial junctions is the prelude for the transmigration process in which tumour cells can move through the junctions between adjacent endothelial cells thereby enabling metastatic seeding in the invaded organs 8 . This process is related to the well-studied physiological process of paracellular diapedesis of leukocytes during inflammation and requires disruption of the barrier function of the endothelium 9 .…”

mentioning

confidence: 99%

“…The vascular endothelial cadherin (VE-cadherin) represents one of the major adhesion systems that support the endothelial barrier function. Signalling pathways that increase vascular permeability generally affect adhesive function of VE-cadherin, in part, through tyrosine phosphorylation of constituents of adherens junctions and activation of acto-myosin contractibility accompanied by reorganization of the actin cytoskeleton that cause formation of stress fibrer and intercellular gaps 8,12 .…”

mentioning

confidence: 99%

See 3 more Smart Citations

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

et al. 2015

View full text Add to dashboard Cite

Disruption of the endothelial barrier by tumour-derived secreted factors is a critical step in cancer cell extravasation and metastasis. Here, by comparative proteomic analysis of melanoma secretomes, we identify the matricellular protein SPARC as a novel tumour-derived vascular permeability factor. SPARC deficiency abrogates tumour-initiated permeability of lung capillaries and prevents extravasation, whereas SPARC overexpression enhances vascular leakiness, extravasation and lung metastasis. SPARC-induced paracellular permeability is dependent on the endothelial VCAM1 receptor and p38 MAPK signalling. Blocking VCAM1 impedes melanoma-induced endothelial permeability and extravasation. The clinical relevance of our findings is highlighted by high levels of SPARC detected in tumour from human pulmonary melanoma lesions. Our study establishes tumour-produced SPARC and VCAM1 as regulators of cancer extravasation, revealing a novel targetable interaction for prevention of metastasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Tumor cell extravasation is one of the critical, and possibly rate-limiting, steps in the process by which cancer spreads to metastatic sites from a primary tumor (1,2). Although we know relatively little about the details of extravasation, recent in vitro studies have elucidated a process beginning with tumor cell arrest in the microcirculation and the formation of protrusions that reach across the endothelial monolayer, accompanied by polarization of tumor cell actin and activation of b-1 integrins to generate firm adhesions (3,4).…”

Section: Introductionmentioning

confidence: 99%

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Cao

Moeendarbary

Isermann

et al. 2016

Biophysical Journal

113

156

View full text Add to dashboard Cite

It is now evident that the cell nucleus undergoes dramatic shape changes during important cellular processes such as cell transmigration through extracellular matrix and endothelium. Recent experimental data suggest that during cell transmigration the deformability of the nucleus could be a limiting factor, and the morphological and structural alterations that the nucleus encounters can perturb genomic organization that in turn influences cellular behavior. Despite its importance, a biophysical model that connects the experimentally observed nuclear morphological changes to the underlying biophysical factors during transmigration through small constrictions is still lacking. Here, we developed a universal chemomechanical model that describes nuclear strains and shapes and predicts thresholds for the rupture of the nuclear envelope and for nuclear plastic deformation during transmigration through small constrictions. The model includes actin contraction and cytosolic back pressure that squeeze the nucleus through constrictions and overcome the mechanical resistance from deformation of the nucleus and the constrictions. The nucleus is treated as an elastic shell encompassing a poroelastic material representing the nuclear envelope and inner nucleoplasm, respectively. Tuning the chemomechanical parameters of different components such as cell contractility and nuclear and matrix stiffnesses, our model predicts the lower bounds of constriction size for successful transmigration. Furthermore, treating the chromatin as a plastic material, our model faithfully reproduced the experimentally observed irreversible nuclear deformations after transmigration in lamin-A/C-deficient cells, whereas the wild-type cells show much less plastic deformation. Along with making testable predictions, which are in accord with our experiments and existing literature, our work provides a realistic framework to assess the biophysical modulators of nuclear deformation during cell transmigration.

show abstract

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria‐related pathways in colorectal cancer

Everest‐Dass,

Nersisyan,

Maar

et al. 2023

Molecular Oncology

View full text Add to dashboard Cite

Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients. CD44 isoform 4 indicated poor outcome and correlated with epithelial‐mesenchymal transition (EMT) and decreased oxidative phosphorylation in patients; opposite associations were found for isoform 3. Pan‐CD44 knockdown (kd) independently impaired primary tumor formation and abrogated distant metastasis in CRC xenografts. The xenograft tumors mainly expressed the clinically relevant CD44 isoforms 3 and 4. Both isoforms were enhanced in the paranecrotic, hypoxic tumor regions but were generally absent in lung metastases. Upon CD44 kd, tumor angiogenesis was increased in the paranecrotic areas, accompanied by reduced HIF‐1α and CEACAM5 but increased E‐cadherin expression. Mitochondrial genes and proteins were induced upon pan‐CD44 kd, as were oxidative phosphorylation genes. Hypoxia increased VEGF release from tumor spheres, particularly upon CD44 kd. Genes affected upon CD44 kd in xenografts specifically overlapped concordantly with genes correlating with CD44 isoform 4 (but not isoform 3) in patients, validating the clinical relevance of the used model and highlighting the metastasis‐promoting role of CD44 isoform 4.

show abstract

Crossing the endothelial barrier during metastasis

Cited by 734 publications

References 144 publications

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria‐related pathways in colorectal cancer

Contact Info

Product

Resources

About