Identification of SPP1+ macrophages in promoting cancer stemness via vitronectin and CCL15 signals crosstalk in liver cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Researchers discovered a specific macrophage type (SPP1+) that fuels liver cancer growth and resistance to therapy. Targeting this macrophage-tumor feedback loop offers a new therapeutic strategy for liver cancer.
Area Of Science
- Cancer Biology
- Immunology
- Oncology
Background
- Macrophages have dual roles in cancer, influencing both progression and suppression.
- Understanding macrophage polarization and function is key for developing effective cancer therapies.
Purpose Of The Study
- To identify macrophage subpopulations involved in liver cancer progression.
- To elucidate the mechanisms by which these macrophages promote tumor stemness and chemoresistance.
Main Methods
- Analysis of single-cell RNA sequencing data from liver cancer patients.
- Investigation of macrophage-tumor cell interactions and signaling pathways.
- Evaluation of therapeutic targeting of identified pathways.
Main Results
- Identified a SPP1+ macrophage subpopulation associated with poor liver cancer prognosis.
- SPP1+ macrophages induce tumor stemness via a vitronectin (VTN)-dependent pathway (integrin αvβ5/AMPK/YAP1/SOX4).
- CCL15 drives M0 macrophage polarization to SPP1+ phenotype, creating a feedback loop; SPP1+ macrophages confer chemoresistance.
Conclusions
- SPP1+ macrophages are critical drivers of liver cancer progression and chemoresistance.
- Targeting the SPP1+ macrophage-tumor feedback loop, specifically the integrin αvβ5/YAP1 axis, sensitizes liver cancer to chemotherapy.
- This study provides novel therapeutic targets for liver cancer treatment.
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