Extracellular vesicles from ovarian cancer cells induce senescent lipid-laden macrophages to facilitate omental metastasis
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View abstract on PubMed
Summary
This summary is machine-generated.Ovarian cancer cells use extracellular vesicles (EVs) to reprogram omental macrophages, promoting metastasis. Targeting CD36 and senescent cells may offer new ovarian cancer therapies.
Area Of Science
- Oncology
- Cell Biology
- Metabolism
Background
- Ovarian cancer frequently metastasizes to the omentum, involving lipid-laden macrophages.
- Mechanisms of macrophage reprogramming and their role in omental metastasis are not fully understood.
- Extracellular vesicles (EVs) are implicated in tumor-stroma interactions during metastasis.
Purpose Of The Study
- To investigate how ovarian cancer-derived EVs influence macrophages and adipocytes in the omentum.
- To elucidate the role of EVs in promoting omental metastasis.
- To explore potential therapeutic strategies targeting EV-mediated processes.
Main Methods
- Single-cell transcriptomics and proteomics of ovarian cancer cells and EVs.
- In vivo mouse models of ovarian cancer metastasis.
- Patient-derived omentum-macrophage co-culture systems.
- Lipidomic profiling, lipid staining, and senescence assays.
- Immunohistochemistry of clinical specimens.
Main Results
- EVs from metastatic ovarian cancer cells reprogram macrophages, inducing lipid accumulation and a pro-metastatic phenotype.
- Tumor EVs stimulate omental adipocytes to release lipids, which are taken up by macrophages via CD36.
- This process leads to macrophage senescence and the development of a pro-metastatic secretory phenotype.
- CD36 overexpression correlates with omental metastasis and poor survival.
- CD36 inhibition and senolytic therapy reduced omental metastasis in vivo.
Conclusions
- Ovarian cancer metastasis to the omentum is driven by an EV-mediated mechanism.
- EVs promote lipid-laden senescent macrophages through CD36-dependent lipid uptake, altering the metastatic niche.
- Targeting CD36 and senescent cells presents a promising therapeutic avenue for ovarian cancer omental metastasis.
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