کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10901030 1084678 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
12(S)-HETE increases intracellular Ca2+ in lymph-endothelial cells disrupting their barrier function in vitro; stabilization by clinical drugs impairing calcium supply
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
12(S)-HETE increases intracellular Ca2+ in lymph-endothelial cells disrupting their barrier function in vitro; stabilization by clinical drugs impairing calcium supply
چکیده انگلیسی
Secretion of 12(S)-HETE by breast cancer emboli provokes “circular chemorepellent induced defects” (CCIDs) in the adjacent lymphatic vasculature facilitating their intravasation and lymph node metastasis which determines prognosis. Therefore, elucidating the mechanism of lymph endothelial cell (LEC) wall disintegration may provide cues for anti-metastatic intervention. The role of intracellular free Ca2+ for CCID formation was investigated in LECs using MCF-7 or MDA-MB231 breast cancer cell spheroids in a three-dimensional cell co-culture model. 12(S)-HETE elevated the Ca2+ level in LEC by activating PLC/IP3. Downstream, the Ca2+-calmodulin kinase MYLK contributed to the phosphorylation of Ser19-MLC2, LEC contraction and CCID formation. Approved clinical drugs, lidoflazine, ketotifen, epiandrosterone and cyclosporine, which reportedly disturb cellular calcium supply, inhibited 12(S)-HETE-induced Ca2+ increase, Ser19-MLC2 phosphorylation and CCID formation. This treatment strategy may reduce spreading of breast cancer through lymphatics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 380, Issue 1, 28 September 2016, Pages 174-183
نویسندگان
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