Exosomal HMGB1 Promoted Cancer Malignancy
Reciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/4/877 |
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| author | Jiaan-Der Wang Ya-Yu Wang Shih-Yi Lin Cheng-Yi Chang Jian-Ri Li Shi-Wei Huang Wen-Ying Chen Su-Lan Liao Chun-Jung Chen |
| author_facet | Jiaan-Der Wang Ya-Yu Wang Shih-Yi Lin Cheng-Yi Chang Jian-Ri Li Shi-Wei Huang Wen-Ying Chen Su-Lan Liao Chun-Jung Chen |
| author_sort | Jiaan-Der Wang |
| collection | DOAJ |
| description | Reciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released into the extracellular space, partly in their exosomal form. High-mobility group box 1 (HMGB1) is a type of exosomal cargo, and the antiplatelet drugs aspirin and dipyridamole interfered with its incorporation into the exosomes. Those released substances and exosomes, along with exogenous HMGB1, promoted cancer cell survival and protected cells from doxorubicin cytotoxicity. In a tumor-bearing model established using murine Lewis lung carcinoma (LLC) cells and C57BL/6 mice, the tumor suppressive effect of dipyridamole correlated well with decreased circulating white blood cells, soluble P-selectin, TGF-β1 (Transforming Growth Factor-β1), exosomes, and exosomal HMGB1, as well as tumor platelet infiltration. Exosome release inhibitor GW4869 exhibited suppressive effects as well. The suppressive effect of dipyridamole on cancer cell survival was paralleled by a reduction of HMGB1/receptor for advanced glycation end-products axis, and proliferation- and migration-related β-catenin, Yes-associated protein 1, Runt-related transcription factor 2, and TGF- β1/Smad signals. Therefore, exosomes and exosomal HMGB1 appear to have roles in platelet-driven cancer malignancy and represent targets of antiplatelet drugs in anticancer treatment. |
| first_indexed | 2024-03-09T00:44:56Z |
| format | Article |
| id | doaj.art-abf039a9900d4d5d8e840abf64968af4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T00:44:56Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-abf039a9900d4d5d8e840abf64968af42023-12-11T17:37:34ZengMDPI AGCancers2072-66942021-02-0113487710.3390/cancers13040877Exosomal HMGB1 Promoted Cancer MalignancyJiaan-Der Wang0Ya-Yu Wang1Shih-Yi Lin2Cheng-Yi Chang3Jian-Ri Li4Shi-Wei Huang5Wen-Ying Chen6Su-Lan Liao7Chun-Jung Chen8Children’s Medical Center, Taichung Veterans General Hospital, Taichung City 407, TaiwanDepartment of Family Medicine, Taichung Veterans General Hospital, Taichung City 407, TaiwanInstitute of Clinical Medicine, National Yang Ming University, Taipei City 112, TaiwanDepartment of Surgery, Feng Yuan Hospital, Taichung City 420, TaiwanDivision of Urology, Taichung Veterans General Hospital, Taichung City 407, TaiwanTranslational Cell Therapy Center, China Medical University Hospital, Taichung City 404, TaiwanDepartment of Veterinary Medicine, National Chung Hsing University, Taichung City 402, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung City 407, TaiwanDepartment of Medical Research, Taichung Veterans General Hospital, Taichung City 407, TaiwanReciprocal crosstalk between platelets and malignancies underscores the potential of antiplatelet therapy in cancer treatment. In this study, we found that human chronic myeloid leukemia K562 cell-differentiated megakaryocytes and murine platelets produced bioactive substances and these are released into the extracellular space, partly in their exosomal form. High-mobility group box 1 (HMGB1) is a type of exosomal cargo, and the antiplatelet drugs aspirin and dipyridamole interfered with its incorporation into the exosomes. Those released substances and exosomes, along with exogenous HMGB1, promoted cancer cell survival and protected cells from doxorubicin cytotoxicity. In a tumor-bearing model established using murine Lewis lung carcinoma (LLC) cells and C57BL/6 mice, the tumor suppressive effect of dipyridamole correlated well with decreased circulating white blood cells, soluble P-selectin, TGF-β1 (Transforming Growth Factor-β1), exosomes, and exosomal HMGB1, as well as tumor platelet infiltration. Exosome release inhibitor GW4869 exhibited suppressive effects as well. The suppressive effect of dipyridamole on cancer cell survival was paralleled by a reduction of HMGB1/receptor for advanced glycation end-products axis, and proliferation- and migration-related β-catenin, Yes-associated protein 1, Runt-related transcription factor 2, and TGF- β1/Smad signals. Therefore, exosomes and exosomal HMGB1 appear to have roles in platelet-driven cancer malignancy and represent targets of antiplatelet drugs in anticancer treatment.https://www.mdpi.com/2072-6694/13/4/877antiplateletexosomeHMGB1malignancy |
| spellingShingle | Jiaan-Der Wang Ya-Yu Wang Shih-Yi Lin Cheng-Yi Chang Jian-Ri Li Shi-Wei Huang Wen-Ying Chen Su-Lan Liao Chun-Jung Chen Exosomal HMGB1 Promoted Cancer Malignancy Cancers antiplatelet exosome HMGB1 malignancy |
| title | Exosomal HMGB1 Promoted Cancer Malignancy |
| title_full | Exosomal HMGB1 Promoted Cancer Malignancy |
| title_fullStr | Exosomal HMGB1 Promoted Cancer Malignancy |
| title_full_unstemmed | Exosomal HMGB1 Promoted Cancer Malignancy |
| title_short | Exosomal HMGB1 Promoted Cancer Malignancy |
| title_sort | exosomal hmgb1 promoted cancer malignancy |
| topic | antiplatelet exosome HMGB1 malignancy |
| url | https://www.mdpi.com/2072-6694/13/4/877 |
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