Detail of Figure5C_Mixed_WT_Ptgs1Ptgs2KO_N3



Project
Title
Live imaging of the dynamics of intracellular Ca2+ concentration in Ptgs1/Ptgs2-/- BrafV600E melanoma cells mixed with parental BrafV600E melanoma implanted ipsilaterally.
Description
Live imaging of the dynamics of intracellular Ca2+ concentration in Ptgs1/Ptgs2-/- BrafV600E melanoma cells mixed with parental BrafV600E melanoma implanted ipsilaterally.
Release, Updated
2023-02-21
License
CC BY
Kind
Image data
File Formats
.oib
Data size
415.8 MB

Organism
Mus musculus ( NCBI:txid10090 )
Strain(s)
-
Cell Line
BrafV600E cell
Gene symbols
Ptgs1, Ptgs2

Datatype
-
Molecular Function (MF)
G protein-coupled receptor binding ( GO:0001664 )
Biological Process (BP)
Cellular Component (CC)
Biological Imaging Method
time lapse microscopy ( Fbbi:00000249 )
X scale
0.552 micrometer/pixel
Y scale
0.552 micrometer/pixel
Z scale
1 micrometer/slice
T scale
3 sec per time interval

Image Acquisition
Experiment type
-
Microscope type
-
Acquisition mode
-
Contrast method
-
Microscope model
-
Detector model
-
Objective model
-
Filter set
-

Summary of Methods
See details in Konishi Y, et. al. (2021) Cancer Res, 2021 Aug 1;81(15):4124-4132.
Related paper(s)

Yoshinobu Konishi, Hiroshi Ichise, Tetsuya Watabe, Choji Oki, Shinya Tsukiji, Yoko Hamazaki, Yasuhiro Murakawa, Akifumi Takaori-Kondo, Kenta Terai, Michiyuki Matsuda (2021) Intravital Imaging Identifies the VEGF-TXA2 Axis as a Critical Promoter of PGE2 Secretion from Tumor Cells and Immune Evasion., Cancer research, Volume 81, Number 15, pp. 4124-4132

Published in 2021 Aug 1 (Electronic publication in May 25, 2021, midnight )

(Abstract) Prostaglandin E2 (PGE2) promotes tumor progression through evasion of antitumor immunity. In stark contrast to cyclooxygenase-dependent production of PGE2, little is known whether PGE2 secretion is regulated within tumor tissues. Here, we show that VEGF-dependent release of thromboxane A2 (TXA2) triggers Ca(2+) transients in tumor cells, culminating in PGE2 secretion and subsequent immune evasion in the early stages of tumorigenesis. Ca(2+) transients caused cPLA2 activation and triggered the arachidonic acid cascade. Ca(2+) transients were monitored as the surrogate marker of PGE2 secretion. Intravital imaging of Braf(V600E) mouse melanoma cells revealed that the proportion of cells exhibiting Ca(2+) transients is markedly higher in vivo than in vitro. The TXA2 receptor was indispensable for the Ca(2+) transients in vivo, high intratumoral PGE2 concentration, and evasion of antitumor immunity. Notably, treatment with a VEGF receptor antagonist and an anti-VEGF antibody rapidly suppressed Ca(2+) 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. SIGNIFICANCE: This study identifies the VEGF-TXA2 axis as a potentially targetable regulator of PGE2 secretion, which provides novel strategies for prevention and treatment of multiple types of malignancies.
(MeSH Terms)

Contact
Kenta Terai , kyoto University , Graduate School of Medicine , Department of Pathology and Biology of Diseases
Contributors

OMERO Dataset
OMERO Project
Source