1
40
2
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1073/pnas.1817325115" target="_blank" rel="noreferrer noopener">http://doi.org/10.1073/pnas.1817325115</a>
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
199-204
Issue
1
Volume
116
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Cysteinyl leukotriene 2 receptor promotes endothelial permeability, tumor angiogenesis, and metastasis.
Publisher
An entity responsible for making the resource available
Proceedings of the National Academy of Sciences of the United States of America
Date
A point or period of time associated with an event in the lifecycle of the resource
2019
2019-01
Subject
The topic of the resource
*angiogenesis; *cysteinyl leukotriene receptors; *endothelial cells; *metastasis; *tumor growth; Male; Animals; Mice; Gene Knockout Techniques; Lung Neoplasms/drug therapy; Neoplasm Transplantation; Neoplasms; Receptors; Inbred C57BL; Neovascularization; Experimental; Capillary Permeability/drug effects; Cyclohexanecarboxylic Acids/pharmacology; Endothelial Cells/*drug effects; Leukotriene Antagonists/pharmacology; Neoplasm Metastasis/drug therapy; Phthalic Acids/pharmacology; Leukotriene/drug effects/*metabolism; Pathologic/*chemically induced/drug therapy
Creator
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Duah Ernest; Teegala Lakshminarayan Reddy; Kondeti Vinay; Adapala Ravi K; Keshamouni Venkateshwar G; Kanaoka Yoshihide; Austen K Frank; Thodeti Charles K; Paruchuri Sailaja
Description
An account of the resource
Cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators that enhance vascular permeability through distinct receptors (CysLTRs). We found that CysLT2R regulates angiogenesis in isolated mouse endothelial cells (ECs) and in Matrigel implants in WT mice and enhances EC contraction and permeability via the Rho-dependent myosin light chain 2 and vascular endothelial (VE)-cadherin axis. Since solid tumors utilize aberrant angiogenesis for their growth and metastasis and their vessels exhibit vascular hyperpermeability, we hypothesized that CysLT2R, via its actions on the endothelium, might regulate tumor growth. Both tumor growth and metastases of adoptively transferred syngeneic Lewis lung carcinoma (LLC) cells are significantly reduced in CysLT2R-null mice (Cysltr2 (-/-)) compared with WT and CysLT1R-null mice (Cysltr1 (-/-)). In WT recipients of LLC cells, CysLT2R expression is significantly increased in the tumor vasculature, compared with CysLT1R. Further, the tumor vasculature in Cysltr2 (-/-) recipients exhibited significantly improved integrity, as revealed by increased pericyte coverage and decreased leakage of i.v.-administered Texas Red-conjugated dextran. Administration of a selective CysLT2R antagonist significantly reduced LLC tumor volume, vessel density, dextran leakage, and metastases in WT mice, highlighting CysLT2R as a VEGF-independent regulator of the vasculature promoting risk of metastasis. Thus, both genetic and pharmacological findings establish CysLT2R as a gateway for angiogenesis and EC dysregulation in vitro and ex vivo and in an in vivo model with a mouse tumor. Our data suggest CysLT2R as a possible target for intervention.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1073/pnas.1817325115" target="_blank" rel="noreferrer noopener">10.1073/pnas.1817325115</a>
*angiogenesis
*cysteinyl leukotriene receptors
*endothelial cells
*metastasis
*tumor growth
2019
Adapala Ravi K
Animals
Austen K Frank
Capillary Permeability/drug effects
Cyclohexanecarboxylic Acids/pharmacology
Department of Integrative Medical Sciences
Duah Ernest
Endothelial Cells/*drug effects
Experimental
Gene Knockout Techniques
Inbred C57BL
Kanaoka Yoshihide
Keshamouni Venkateshwar G
Kondeti Vinay
Leukotriene Antagonists/pharmacology
Leukotriene/drug effects/*metabolism
Lung Neoplasms/drug therapy
Male
Mice
NEOMED College of Medicine
Neoplasm Metastasis/drug therapy
Neoplasm Transplantation
Neoplasms
Neovascularization
Paruchuri Sailaja
Pathologic/*chemically induced/drug therapy
Phthalic Acids/pharmacology
Proceedings of the National Academy of Sciences of the United States of America
Receptors
Teegala Lakshminarayan Reddy
Thodeti Charles K
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1073/pnas.1817325115" target="_blank" rel="noreferrer noopener">http://doi.org/10.1073/pnas.1817325115</a>
Pages
199–204
Issue
1
Volume
116
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Cysteinyl leukotriene 2 receptor promotes endothelial permeability, tumor angiogenesis, and metastasis.
Publisher
An entity responsible for making the resource available
Proceedings of the National Academy of Sciences of the United States of America
Date
A point or period of time associated with an event in the lifecycle of the resource
2019
2019-01
Subject
The topic of the resource
*angiogenesis; *cysteinyl leukotriene receptors; *endothelial cells; *metastasis; *tumor growth
Creator
An entity primarily responsible for making the resource
Duah Ernest; Teegala Lakshminarayan Reddy; Kondeti Vinay; Adapala Ravi K; Keshamouni Venkateshwar G; Kanaoka Yoshihide; Austen K Frank; Thodeti Charles K; Paruchuri Sailaja
Description
An account of the resource
Cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators that enhance vascular permeability through distinct receptors (CysLTRs). We found that CysLT2R regulates angiogenesis in isolated mouse endothelial cells (ECs) and in Matrigel implants in WT mice and enhances EC contraction and permeability via the Rho-dependent myosin light chain 2 and vascular endothelial (VE)-cadherin axis. Since solid tumors utilize aberrant angiogenesis for their growth and metastasis and their vessels exhibit vascular hyperpermeability, we hypothesized that CysLT2R, via its actions on the endothelium, might regulate tumor growth. Both tumor growth and metastases of adoptively transferred syngeneic Lewis lung carcinoma (LLC) cells are significantly reduced in CysLT2R-null mice (Cysltr2 (-/-)) compared with WT and CysLT1R-null mice (Cysltr1 (-/-)). In WT recipients of LLC cells, CysLT2R expression is significantly increased in the tumor vasculature, compared with CysLT1R. Further, the tumor vasculature in Cysltr2 (-/-) recipients exhibited significantly improved integrity, as revealed by increased pericyte coverage and decreased leakage of i.v.-administered Texas Red-conjugated dextran. Administration of a selective CysLT2R antagonist significantly reduced LLC tumor volume, vessel density, dextran leakage, and metastases in WT mice, highlighting CysLT2R as a VEGF-independent regulator of the vasculature promoting risk of metastasis. Thus, both genetic and pharmacological findings establish CysLT2R as a gateway for angiogenesis and EC dysregulation in vitro and ex vivo and in an in vivo model with a mouse tumor. Our data suggest CysLT2R as a possible target for intervention.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1073/pnas.1817325115" target="_blank" rel="noreferrer noopener">10.1073/pnas.1817325115</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*angiogenesis
*cysteinyl leukotriene receptors
*endothelial cells
*metastasis
*tumor growth
2019
Adapala Ravi K
Austen K Frank
Department of Integrative Medical Sciences
Duah Ernest
Kanaoka Yoshihide
Keshamouni Venkateshwar G
Kondeti Vinay
NEOMED College of Medicine
Paruchuri Sailaja
Proceedings of the National Academy of Sciences of the United States of America
Teegala Lakshminarayan Reddy
Thodeti Charles K