Vascular Endothelial Growth Factor C Disrupts the Endothelial Lymphatic Barrier to Promote Colorectal Cancer Invasion

Tacconi, Carlotta; Correale, Carmen; Gandelli, Alessandro; Spinelli, Antonino; Dejana, Elisabetta; D’Alessio, Silvia; Danese, Silvio

doi:10.1053/j.gastro.2015.03.005

Cited by 121 publications

(114 citation statements)

References 45 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…VEGF-C, a lymphatic vessel-specific growth factor, is upregulated in various human cancers, including bladder cancer (47)(48)(49), and has been shown to play critical roles in disrupting the endothelial lymphatic barrier (50,51) and facilitating lymphatic invasion of cancer cells, ultimately resulting in significantly enhanced lymphatic metastasis and cancer treatment failure (52). Blocking the VEGF-C/VEGFR-3 lymphangiogenic axis significantly reduces the rate of LN metastasis in multiple cancer-bearing experimental mouse models (17,44,53).…”

Section: Methodsmentioning

confidence: 99%

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Wang¹,

Zhong²,

Jiang³

et al. 2018

Journal of Clinical Investigation

157

151

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Wang¹,

Zhong²,

Jiang³

et al. 2018

Journal of Clinical Investigation

157

151

View full text Add to dashboard Cite

“…It is tempting to hypothesize that expression of specific ligands may mediate the adhesion of tumor cells to macrophages expressing ICAM-1, further increasing liver colonization by circulating cancer cells. Additionally, tumor-activated KCs, and HSCs, which also express ICAM-1 when activated by inflammatory factors (74), further stimulate the expression of ICAM-1 on the surface of endothelial cells, increasing vascular permeability, which is also associated with an increase in tumor cell invasion into a target organ (75).…”

Section: Tumor Cell Adhesion: Lending Tumor Cells a Handmentioning

confidence: 99%

Role of liver ICAM-1 in metastasis

2017

View full text Add to dashboard Cite

Abstract. Intercellular adhesion molecule (ICAM)-1, is a transmembrane glycoprotein of the immunoglobulin (Ig)-like superfamily, consisting of five extracellular Ig-like domains, a transmembrane domain and a short cytoplasmic tail. ICAM-1 is expressed in various cell types, including endothelial cells and leukocytes, and is involved in several physiological processes. Furthermore, it has additionally been reported to be expressed in various cancer cells, including melanoma, colorectal cancer and lymphoma. The majority of studies to date have focused on the expression of the ICAM-1 on the surface of tumor cells, without research into ICAM-1 expression at sites of metastasis. Cancer cells frequently metastasize to the liver, due to its unique physiology and specialized liver sinusoid capillary network. Liver sinusoidal endothelial cells constitutively express ICAM-1, which is upregulated under inflammatory conditions. Furthermore, liver ICAM-1 may be important during the development of liver metastasis. Therefore, it is necessary to improve the understanding of the mechanisms mediated by this adhesion molecule in order to develop host-directed anticancer therapies.

show abstract

“…High HOXD10 expression resulted in abnormal junctions and increased permeability, whereas HOXD10 depletion resulted in reduced permeability through LEC monolayers. Currently, the role of VEGFR-3 signaling in regulating LEC permeability in vitro is not entirely clear, with some reports showing a reduction in transendothelial electric resistance of LECs after stimulation with VEGF-C (Breslin et al, 2007;Tacconi et al, 2015), whereas others found no effect of VEGF-C156S on macromolecular permeability (Cromer et al, 2014). Therefore, it is possible that wild-type VEGF-C induces permeability by activating VEGFR-2, whereas specific VEGFR-3 activation by VEGF-C156S has no such effects.…”

Section: Discussionmentioning

confidence: 99%

“…VEGF-C induces lymphatic permeability both in vitro and in vivo, and facilitates cancer dissemination through the lymphatic system (Breslin et al, 2007;Tacconi et al, 2015). We therefore decided to investigate the role of HOXD10 in lymphatic permeability using two established in vitro methods, transwell LEC permeability for a macromolecular fluorescent tracer (70-kDa FITC-dextran) and transendothelial electric resistance.…”

Section: Hoxd10 Regulates Lec Permeabilitymentioning

confidence: 99%

DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C

Klein

Mathelier

Chong

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Lymphangiogenesis plays a crucial role during development, in cancer metastasis and in inflammation. Activation of VEGFR-3 (also known as FLT4) by VEGF-C is one of the main drivers of lymphangiogenesis, but the transcriptional events downstream of VEGFR-3 activation are largely unknown. Recently, we identified a wave of immediate early transcription factors that are upregulated in human lymphatic endothelial cells (LECs) within the first 30 to 80 min after VEGFR-3 activation. Expression of these transcription factors must be regulated by additional pre-existing transcription factors that are rapidly activated by VEGFR-3 signaling. Using transcription factor activity analysis, we identified the homeobox transcription factor HOXD10 to be specifically activated at early time points after VEGFR-3 stimulation, and to regulate expression of immediate early transcription factors, including NR4A1. Gain-and loss-offunction studies revealed that HOXD10 is involved in LECs migration and formation of cord-like structures. Furthermore, HOXD10 regulates expression of VE-cadherin, claudin-5 and NOS3 (also known as e-NOS), and promotes lymphatic endothelial permeability. Taken together, these results reveal an important and unanticipated role of HOXD10 in the regulation of VEGFR-3 signaling in lymphatic endothelial cells, and in the control of lymphangiogenesis and permeability.

show abstract

Vascular Endothelial Growth Factor C Disrupts the Endothelial Lymphatic Barrier to Promote Colorectal Cancer Invasion

Cited by 121 publications

References 45 publications

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis

Role of liver ICAM-1 in metastasis

DeepCAGE transcriptomics identify HOXD10 as a transcription factor regulating lymphatic endothelial responses to VEGF-C

Contact Info

Product

Resources

About