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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Published in:International journal of molecular sciences 2022-09, Vol.23 (17), p.9596
Main Authors: 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
Format: Article
Language:English
Subjects:
Apoptosis
Aspirin
Blood platelets
Blood vessels
Cancer therapies
Cell death
Cell growth
Cell proliferation
Clinical trials
Clopidogrel
Colon
Colon cancer
Colorectal cancer
Experiments
Gene expression
Metastases
Metastasis
Mortality
Motility
Patients
Senescence
Solid tumors
Tumors
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23179596