Tumor Endothelial Cells

Dudley, Andrew C.

doi:10.1101/cshperspect.a006536

Cited by 343 publications

(263 citation statements)

References 154 publications

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“…In short, these signatures likely represent a tumor endothelium that is increasingly thought of as angiogenically active and chronically inflamed (36). This is in contrast to our signature score that is derived from a physiologically normal microvasculature and as such is highly expressed in low-risk tumors.…”

Section: Discussionmentioning

confidence: 93%

An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors

Tobin

Wennmalm

Lindström

et al. 2016

Clinical Cancer Research

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Purpose: The ability of vascular genes to provide treatment predictive information in breast cancer patients remains unclear. As such, we assessed the expression of genes representative of normal endothelial microvasculature (MV) in relation to treatment-specific patient subgroups.Experimental Design: We used expression data from 993 breast tumors to assess 57 MV genes (summarized to yield an MV score) as well as the genomic grade index (GGI) and PAM50 signatures. MV score was compared with CD31 staining by correlation and gene ontology (GO) analysis, along with clinicopathologic characteristics and PAM50 subtypes. Uni-, multivariate, and/or t-test analyses were performed in all and treatment-specific subgroups, along with a clinical trial cohort of patients with metastatic breast cancer, seven of whom received antiangiogenic therapy.Results: MV score did not correlate with microvessel density (correlation ¼ 0.096), but displayed enrichment for angiogenic GO terms, and was lower in Luminal B tumors. In endocrinetreated patients, a high MV score was associated with decreased risk of metastasis [HR 0.58; 95% confidence interval (CI), 0.38-0.89], even after adjusting for histologic grade, but not GGI or PAM50. Subgroup analysis showed the prognostic strength of the MV score resided in low genomic grade tumors and MV score was significantly increased in metastatic breast tumors after treatment with sunitinib þ docetaxel (P ¼ 0.031).Conclusions: MV score identifies two groups of better and worse survival in low-risk endocrine-treated breast cancer patients. We also show normalization of tumor vasculature on a transcriptional level in response to an angiogenic inhibitor in human breast cancer samples.

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Section: Discussionmentioning

confidence: 93%

An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors

Tobin

Wennmalm

Lindström

et al. 2016

Clinical Cancer Research

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“…The hybrid tip/stalk phenotype, obtained under high levels of Jagged, is reminiscent of and might correspond to the tip-like thin cytoplasmic projections that extend across the vessel lumen of the tumor endothelium but not necessarily a nontumor endothelium (25). (26)(27)(28).…”

Section: Resultsmentioning

confidence: 99%

“…The increased NotchJagged signaling in tumor environment can be attributed to multiple specific traits of tumor endothelial cells (TECs): (i) they can secrete Jagged in the stroma (48) that can potentially activate Notch-Jagged signaling in neighboring endothelium; (ii) they have a proinflammatory gene expression and the inflammation response regulators such as NF-κB and TNF-α can increase Jagged in them (14,49); and (iii) they often adhere to inflammatory cells such as macrophages (25) that can increase Jagged in them via paracrine or juxtacrine signaling. Such an amplified Notch-Jagged signaling can give rise to hybrid tip/stalk cells that closely resemble the observed tip-like projections of the tumor vessels that might overlap with each other and even form loose connections (25).…”

Section: Discussionmentioning

confidence: 99%

Jagged mediates differences in normal and tumor angiogenesis by affecting tip-stalk fate decision

Boareto

Jolly

Ben‐Jacob

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

103

150

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Angiogenesis is critical during development, wound repair, and cancer progression. During angiogenesis, some endothelial cells adopt a tip phenotype to lead the formation of new branching vessels; the trailing stalk cells proliferate to develop the vessel. Notch and VEGF signaling mediate the selection of these tip endothelial cells. However, how Jagged, a Notch ligand that is overexpressed in cancer, affects angiogenesis remains elusive. Here, by developing a theoretical framework for Notch-Delta-Jagged-VEGF signaling, we found that higher production levels of Jagged destabilizes the tip and stalk cell fates and can give rise to a hybrid tip/stalk phenotype that leads to poorly perfused and chaotic angiogenesis, which is a hallmark of cancer. Consistently, the signaling interactions that restrict Notch-Jagged signaling, such as Fringe, cis-inhibition, and increased production of Delta, stabilize tip and stalk fates and limit the existence of hybrid tip/stalk phenotype. Our results underline how overexpression of Jagged can transform physiological angiogenesis into pathological one.

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“…"Stalk" cells are also involved in formation of intercellular connections and synthesis of basement membrane components in a new vessel. It is worth emphasizing, that blood vessels formed in tumor as a result of sprouting angiogenesis show significant abnormalities of endothelium, as well as of basement membrane [24]. Mostly typical are relaxed intercellular connections and fenestrations in endothelial cells.…”

Section: Figurementioning

confidence: 99%

Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

Knopik-Skrocka

Kręplewska

Jarmołowska-Jurczyszyn

2017

Advances in Cell Biology

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Summary: Blood vessel formation in tumor is defined as tumor angiogenesis. So far, the most known its mechanism is sprouting, which means formation of blood vessels from existing ones, as a result of the proliferation and migration of endothelial cells. The main mitogenic factor of these cells is vascular endothelial growth factor VEGF, acting by VEGFR-2 receptors. Recent studies have provided knowledge about the ability of tumors to form vessel-like structures. The phenomenon was called vascular mimicry. Tumor cells show a high plasticity and they can undergo differentiation to the ones with phenotype similar to endothelial cells. Each of the known tumor angiogenesis mechanisms is a result of many different factors and cell cooperation in tumor microenvironment. Tumor ability to the heterogeneous vascularization forces developing of complex, anti-angiogenic therapy directed to different molecular and cellular targets. Therapies, used so far, often lead to drug-induced hypoxia, which increases tumor cell aggressiveness and metastasis.Keywords: tumor angiogenesis, vasculogenic mimicry, anti-angiogenic strategies, resistance to anti-angiogenic therapy Sprouting angiogenesis -formation via endothelial cells proliferation and migration towards avascular tumor area of new branches of blood vessels Intussusception -formation of blood vessels as a result of intussusception (septum) inside existing blood vessels Co-option -oxygen and nutrients acquire as a result of tumor cells migration along existing blood vessels Vasculogenic mimicry -formation by tumor cells of vessel-like structures, without endothelial cells participation Vasculogenesis -formation of tumor blood vessels de novo, as a result of endothelial progenitor cells recruitment

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Tumor Endothelial Cells

Cited by 343 publications

References 154 publications

An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors

An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors

Jagged mediates differences in normal and tumor angiogenesis by affecting tip-stalk fate decision

Tumor Blood Vessels and Vasculogenic Mimicry – Current Knowledge and Searching for New Cellular/Molecular Targets of Anti-Angiogenic Therapy

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