Reference - Detail
| RRC ID | 65076 |
|---|---|
| Author | Konishi Y, Ichise H, Watabe T, Oki C, Tsukiji S, Hamazaki Y, Murakawa Y, Takaori-Kondo A, Terai K, Matsuda M. |
| Title | Intravital Imaging Identifies the VEGF-TXA2 Axis as a Critical Promoter of PGE2 Secretion from Tumor Cells and Immune Evasion. |
| Journal | Cancer Res |
| Abstract |
Prostaglandin E2 (PGE2) promotes tumor progression through evasion of anti-tumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE2, little is known whether or not PGE2 secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A2 (TXA2) triggers Ca2+ transients in tumor cells, culminating in PGE2 secretion and subsequent immune evasion in the early stages of tumorigenesis. Ca2+ transients caused cPLA2 activation and triggered the arachidonic acid cascade. Ca2+ transients were monitored as the surrogate marker of PGE2 secretion. Intravital imaging of BrafV600E mouse melanoma cells revealed that the proportion of cells exhibiting Ca2+ transients is markedly higher in vivo than in vitro. The TXA2 receptor was indispensable for the Ca2+ transients in vivo, high intra-tumoral PGE2 concentration, and evasion of anti-tumor immunity. Notably, treatment with a vascular endothelial growth factor (VEGF) receptor antagonist and an anti-VEGF antibody rapidly suppressed Ca2+ transients and reduced TXA2 and PGE2 concentrations in tumor tissues. These results identify the VEGF-TXA2 axis as a critical promoter of PGE2-dependent tumor immune evasion, providing a molecular basis underlying the immunomodulatory effect of anti-VEGF therapies. |
| Volume | 81(15) |
| Pages | 4124-4132 |
| Published | 2021-8-1 |
| DOI | 10.1158/0008-5472.CAN-20-4245 |
| PII | 0008-5472.CAN-20-4245 |
| PMID | 34035084 |
| MeSH | Animals Dinoprostone / immunology* Humans Immune Evasion / immunology* Intravital Microscopy / methods* Mice Mice, Nude Vascular Endothelial Growth Factor A / immunology* |
| IF | 9.727 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 16 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MDCK(RCB0995) |