Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis
Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of l...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Won-Tae Kim Jeong-Yeon Mun Seung-Woo Baek Min-Hye Kim Gi-Eun Yang Mi-So Jeong Sun Young Choi Jin-Yeong Han Moo Hyun Kim Sun-Hee Leem |
| author_facet | Won-Tae Kim Jeong-Yeon Mun Seung-Woo Baek Min-Hye Kim Gi-Eun Yang Mi-So Jeong Sun Young Choi Jin-Yeong Han Moo Hyun Kim Sun-Hee Leem |
| author_sort | Won-Tae Kim |
| collection | DOAJ |
| description | Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy. |
| first_indexed | 2024-03-10T01:47:42Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-10T01:47:42Z |
| publishDate | 2022-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fe383b81012941a6a8317fa9706d5a412023-11-23T13:13:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317959610.3390/ijms23179596Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer MetastasisWon-Tae Kim0Jeong-Yeon Mun1Seung-Woo Baek2Min-Hye Kim3Gi-Eun Yang4Mi-So Jeong5Sun Young Choi6Jin-Yeong Han7Moo Hyun Kim8Sun-Hee Leem9Department of Biomedical Sciences, Dong-A University, Busan 49315, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaMetabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaDepartment of Cardiology, Dong-A University Hospital, Busan 49201, KoreaDepartment of Laboratory Medicine, Dong-A University Hospital, Busan 49201, KoreaDepartment of Cardiology, Dong-A University Hospital, Busan 49201, KoreaDepartment of Biomedical Sciences, Dong-A University, Busan 49315, KoreaContrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.https://www.mdpi.com/1422-0067/23/17/9596SERPINE1MMP1cancer metastasisantiplatelet agents |
| spellingShingle | Won-Tae Kim Jeong-Yeon Mun Seung-Woo Baek Min-Hye Kim Gi-Eun Yang Mi-So Jeong Sun Young Choi Jin-Yeong Han Moo Hyun Kim Sun-Hee Leem Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis International Journal of Molecular Sciences SERPINE1 MMP1 cancer metastasis antiplatelet agents |
| title | Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis |
| title_full | Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis |
| title_fullStr | Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis |
| title_full_unstemmed | Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis |
| title_short | Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis |
| title_sort | secretory serpine1 expression is increased by antiplatelet therapy inducing mmp1 expression and increasing colon cancer metastasis |
| topic | SERPINE1 MMP1 cancer metastasis antiplatelet agents |
| url | https://www.mdpi.com/1422-0067/23/17/9596 |
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