Arsenic May Act as a Pro-Metastatic Carcinogen Through Promoting Tumor Cell-Induced Platelet Aggregation
- 주제(키워드) arsenic , carcinogenesis , tumor metastasis , platelet , tumor cell-platelet aggregation
- 주제(기타) Toxicology
- 설명문(일반) [Kim, Keunyoung; Heo, Yoon-Kyung; Chun, Soyoung; Bian, Yiying; Chung, Jin-Ho] Seoul Natl Univ, Coll Pharm, Seoul 08826, South Korea; [Kim, Chang-Hwan] Agcy Def Dev, R&D Inst 5, Daejeon 34186, South Korea; [Bae, Ok-Nam] Hanyang Univ, Coll Pharm, Ansan 15588, Gyeonggido, South Korea; [Lee, Moo-Yeol] Dongguk Univ, Coll Pharm, Goyang 10326, Gyeonggido, South Korea; [Lim, Kyung-Min] Ewha Womans Univ, Coll Pharm, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 OXFORD UNIV PRESS
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160301
- 본문언어 영어
- Published As http://dx.doi.org/10.1093/toxsci/kfy247
- PubMed https://pubmed.ncbi.nlm.nih.gov/30428081
초록/요약
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.
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