کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8434692 | 1546649 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Reprogramming tumor stroma using an endogenous lipid lipoxin A4 to treat pancreatic cancer
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کلمات کلیدی
Lipoxin B4CAFα-SMALXB4TGF-βLXA4PDGFHpSCECMCol1α1Pancreatic ductal adenocarcinoma - آدنوکارسینوم پانکراس داکتالPDAC یا pancreatic ductal adenocarcinoma - آدنوکارسینومای داکتال پانکراسTumor stroma - استروما تومورα-smooth muscle actin - اکتین عضله آلفا صافTransforming growth factor β - تبدیل فاکتور رشد βPancreatic cancer - سرطان پانکراسPancreatic Stellate Cells - سلول های ستون فقرات پانکراسConditioned medium - شرایط محیطیplatelet-derived growth factor - فاکتور رشد حاصل از پلاکتCancer-associated fibroblasts - فیبروبلاست های مرتبط با سرطانcancer-associated fibroblast - فیبروبلاست وابسته به سرطانlipoxin A4 - لیپوکین A4extra cellular matrix - ماتریس سلولی اضافیCol1 - کل 1
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Pancreatic stellate cells (PSCs) are the precursors of cancer-associated fibroblasts (CAFs), which potentiate pancreatic tumor growth and progression. In this study, we investigated whether Lipoxin A4 (LXA4), an endogenous bioactive lipid, can inhibit the differentiation of human PSCs (hPSCs) into CAF-like myofibroblasts and thereby hPSC-induced pro-tumorigenic effects. LXA4 significantly inhibited TGF-β-mediated differentiation of hPSCs by inhibiting pSmad2/3 signalling. Furthermore, treatment with LXA4 abolished the paracrine effects (proliferation and migration of Panc-1 tumor cells) of hPSCs in vitro. These data demonstrated that LXA4 can interrupt pro-tumoral paracrine signalling of hPSCs. Furthermore, LXA4 treatment significant decreased the size and growth rate of 3D-heterospheroids comprised of hPSC and Panc-1 and these effects were exhibited due to inhibition of hPSC-induced collagen1 expression. In vivo, we examined the therapeutic efficacy of LXA4 in a co-injection (Panc-1 and hPSCs) subcutaneous tumor model. Intriguingly, LXA4 significantly abolished the tumor growth (either injected intratumor or intraperitoneally), attributed to a significant reduction in fibrosis, shown with collagen1 expression. Altogether, this study proposes LXA4 as a potent inhibitor for hPSCs which can be applied to reprogram tumor stroma in order to treat pancreatic cancer.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 420, 28 April 2018, Pages 247-258
Journal: Cancer Letters - Volume 420, 28 April 2018, Pages 247-258
نویسندگان
Jonas Schnittert, Marcel A. Heinrich, Praneeth R. Kuninty, Gert Storm, Jai Prakash,