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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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Autores principales: Kim, Won-Tae, Mun, Jeong-Yeon, Baek, Seung-Woo, Kim, Min-Hye, Yang, Gi-Eun, Jeong, Mi-So, Choi, Sun Young, Han, Jin-Yeong, Kim, Moo Hyun, Leem, Sun-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455756/
https://www.ncbi.nlm.nih.gov/pubmed/36076991
http://dx.doi.org/10.3390/ijms23179596
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author Kim, Won-Tae
Mun, Jeong-Yeon
Baek, Seung-Woo
Kim, Min-Hye
Yang, Gi-Eun
Jeong, Mi-So
Choi, Sun Young
Han, Jin-Yeong
Kim, Moo Hyun
Leem, Sun-Hee
author_facet Kim, Won-Tae
Mun, Jeong-Yeon
Baek, Seung-Woo
Kim, Min-Hye
Yang, Gi-Eun
Jeong, Mi-So
Choi, Sun Young
Han, Jin-Yeong
Kim, Moo Hyun
Leem, Sun-Hee
author_sort Kim, Won-Tae
collection PubMed
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.
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spelling pubmed-94557562022-09-09 Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis Kim, Won-Tae Mun, Jeong-Yeon Baek, Seung-Woo Kim, Min-Hye Yang, Gi-Eun Jeong, Mi-So Choi, Sun Young Han, Jin-Yeong Kim, Moo Hyun Leem, Sun-Hee Int J Mol Sci Article 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. MDPI 2022-08-24 /pmc/articles/PMC9455756/ /pubmed/36076991 http://dx.doi.org/10.3390/ijms23179596 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Won-Tae
Mun, Jeong-Yeon
Baek, Seung-Woo
Kim, Min-Hye
Yang, Gi-Eun
Jeong, Mi-So
Choi, Sun Young
Han, Jin-Yeong
Kim, Moo Hyun
Leem, Sun-Hee
Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9455756/
https://www.ncbi.nlm.nih.gov/pubmed/36076991
http://dx.doi.org/10.3390/ijms23179596
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