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| Status |
Public on May 01, 2024 |
| Title |
Malignant ascites microenvironment induced macrophage reprogramming facilities epithelial ovarian cancer peritoneal metastasis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Macrophages form a primary immune cells population in tumor tissues and malignant ascites microenvironment (MAM). They can be activated and polarized into tumor-associated macrophages (TAM) by the embedded environment and promote tumor progression and metastasis However, the molecular mechanisms of MAM in macrophage polarization and the effects on epithelial ovarian cancer (EOC) metastatic progression remain elusive. Here, we found that that MAM modulates RhoA-GTPase-F-actin-Hippo signaling cascade in facilitating M2-like macrophage polarization that, in turn, promotes tumor dissemination. PUFA enriched magligant ascites microenvironment promote macrophage lipid oxidative phosphorylation and supression RhoA-GTPase-Yap1 axis. Genetic ablation Yap1 in macrophage exhibited M2-like polarization and enhanced ovrian tumor dissemination. Pharmacology inhibit Mst1/2 could rescue M2-like TAM polarization in MAM and alter the lipid oxidation of macrophages in MAM, more importantly, inhibit ovarian metastatic properties. Through comparasion primary TAM (P-TAM) and metastasis TAM (M-TAM), we proved that Hippo-Yap1 siganl results M-TAM with high M2/M1 ratio. These findings implicate critical functions of PUFA modulate RhoA-Hippo axis in facility TAM polarization and also suggest manipulation of PUFA metabolism or RhoA-Hippo siganl as a therapeutic strategy aganist EOC metastasis.
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| Overall design |
Macrophages mRNA profiles of M1 macrophages and M1 macrophages treated with OCM , M2 macrophages and M2 macrophages treated with OCM
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| Contributor(s) |
Wang H, Chan D |
| Citation missing |
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| Submission date |
May 25, 2021 |
| Last update date |
May 01, 2024 |
| Contact name |
Huogang WANG |
| E-mail(s) |
wanghuog@hku.hk
|
| Phone |
54238279
|
| Organization name |
The University of Hong Kong
|
| Department |
Obstetrics and Gynecology
|
| Street address |
22 Sassoon Road
|
| City |
Hong Kong |
| State/province |
Not Applicable |
| ZIP/Postal code |
9999 |
| Country |
China |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA732707 |
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