Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact.
Cell Rep
; 20(9): 2072-2086, 2017 Aug 29.
Article
in En
| MEDLINE
| ID: mdl-28854359
ABSTRACT
Vascular normalization in tumors may improve drug delivery and anti-tumor immunity. Angiogenesis inhibitors induce hypoxia, which may facilitate malignant progression; therefore, we investigated other methods to promote vascular maturation. Here, we show that lysophosphatidic acid (LPA) enhances blood flow by promoting fine vascular networks, thereby improving vascular permeability and suppressing tumor growth when combined with anti-cancer drug treatment. Six different G protein-coupled receptors have been identified as LPA receptors (LPA1-6). In studies using mutant mice, we found that LPA4 is involved in vascular network formation. LPA4 activation induces circumferential actin bundling beneath the cell membrane and enhances linear adherens junction formation by VE-cadherin in endothelial cells. Therefore, we conclude that activation of LPA4 is a promising approach for vascular regulation.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Cell Communication
/
Drug Delivery Systems
/
Endothelial Cells
/
Receptors, Lysophosphatidic Acid
/
Neoplasms
/
Neovascularization, Pathologic
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2017
Type:
Article