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Arsenic May Act as a Pro-Metastatic Carcinogen Through Promoting Tumor Cell-Induced Platelet Aggregation

Title
Arsenic May Act as a Pro-Metastatic Carcinogen Through Promoting Tumor Cell-Induced Platelet Aggregation
Author
배옥남
Keywords
arsenic; carcinogenesis; tumor metastasis; platelet; tumor cell-platelet aggregation
Issue Date
2019-03
Publisher
OXFORD UNIV PRESS
Citation
TOXICOLOGICAL SCIENCES, v. 168, No. 1, Page. 18-27
Abstract
Arsenic-associated carcinogenesis and related mortality are a major public health concern worldwide; however, the underlying mechanism of action remains unclear. Here, we demonstrated that arsenic promotes tumor metastasis by stimulating tumor cell-platelet aggregation (TCPA), which can ultimately increase cancer-related mortality. In freshly isolated human platelets in vitro, arsenic potentiated TCPA prompted by diverse cancer cell lines, which was attributable to increased platelet reactivity to TCPA with respect to thrombin generation and P-selectin, GP(IIb/IIIa) expression. Consistently, the co-existence of platelets and arsenic significantly enhanced tumor cell adhesion, extravasation and invasion along with increased metastasis-related markers like metallo-matrix proteinase-2 and -9 in vitro, which was attenuated by platelet activation blockers. Importantly, the exposure to arsenic-contaminated drinking water (2ppm, 3weeks) in mice in vivo significantly increased the metastasis of intravenously injected melanoma cells into lung. Furthermore, the exposure to arsenic-contaminated drinking water significantly reduced the survival of melanoma cell-injected mice, which was attenuated by the pretreatment of platelet-activation blockers; aspirin and eptifibatide. All these results provide an important clue to understand the mechanism underlying arsenic-associated cancer mortality and its prevention.
URI
https://academic.oup.com/toxsci/article/168/1/18/5182299http://repository.hanyang.ac.kr/handle/20.500.11754/112601
ISSN
1096-6080; 1096-0929
DOI
10.1093/toxsci/kfy247
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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