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Exosomal HMGB1 Promoted Cancer Malignancy
Jiaan-Der Wang1,2, Ya-Yu Wang3,4, Shih-Yi Lin4,5
1Children's Medical Center, Taichung Veterans General Hospital, Taichung City 407, Taiwan.
Antiplatelet drugs like dipyridamole inhibit cancer cell survival by reducing exosomal High-Mobility Group Box 1 (HMGB1) release. This targets platelet-driven malignancy and offers new avenues for cancer treatment.
Area of Science:
- Oncology
- Hematology
- Cell Biology
Background:
- Platelets and cancer exhibit reciprocal crosstalk, suggesting antiplatelet therapy's potential in cancer treatment.
- Platelets and megakaryocytes release bioactive substances, including exosomes containing High-Mobility Group Box 1 (HMGB1), into circulation.
Purpose of the Study:
- To investigate the role of platelet-derived exosomes and exosomal HMGB1 in cancer malignancy.
- To evaluate the anti-cancer effects of antiplatelet drugs, specifically dipyridamole, and their impact on exosomal HMGB1.
Main Methods:
- Analysis of bioactive substances and exosomes released by K562 cell-differentiated megakaryocytes and murine platelets.
- In vivo studies using a murine Lewis lung carcinoma (LLC) model treated with dipyridamole and exosome release inhibitor GW4869.
- Assessment of molecular signaling pathways, including HMGB1/RAGE, β-catenin, YAP1, RUNX2, and TGF-β1/Smad.
Main Results:
- Antiplatelet drugs (aspirin, dipyridamole) reduced HMGB1 incorporation into exosomes.
- Exosomes and HMGB1 promoted cancer cell survival and protected against doxorubicin.
- Dipyridamole treatment decreased circulating HMGB1, exosomes, and tumor platelet infiltration, correlating with tumor suppression.
- GW4869 also exhibited suppressive effects on tumor growth.
Conclusions:
- Exosomes and exosomal HMGB1 play a significant role in platelet-driven cancer progression.
- Antiplatelet drugs targeting exosomal HMGB1 represent a promising therapeutic strategy for cancer treatment.
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