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Tilte: Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids.+ t3 G7 k' P8 b4 K
出处：cancer cell5 Q' I0 j2 I1 c
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Abstract: The development of resistance to chemotherapy is a major obstacle for lasting effective treatment of cancer. Here, we demonstrate that endogenous mesenchymal stem cells (MSCs) become activated during treatment with platinum analogs and secrete factors that protect tumor cells against a range of chemotherapeutics. Through a metabolomics approach, we identified two distinct platinum-induced polyunsaturated fatty acids (PIFAs), 12-oxo-5,8,10-heptadecatrienoic acid (KHT) and hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3)), that in minute quantities induce resistance to a broad spectrum of chemotherapeutic agents. Interestingly, blocking central enzymes involved in the production of these PIFAs (cyclooxygenase-1 and thromboxane synthase) prevents MSC-induced resistance. Our findings show that MSCs are potent mediators of resistance to chemotherapy and reveal targets to enhance chemotherapy efficacy in patients. 8 o* d5 T- @! y + r. L5 U" S4 T; _! q: N% j" Q题目：间充质干细胞通过释放铂诱导的脂肪酸 导致化疗耐药。 " n* k0 w) k- I: W摘要：化疗耐药的产生是肿瘤能够有效治疗的一大障碍。这里，我们证明：在应用铂类化疗药治疗时，内源性的MSC会激活，并分泌一些因子保护肿瘤细胞抵抗一系列的化疗药物。通过中间产物组学（metabolomics）的方法，我们坚定了两个铂诱导的多不饱和脂肪酸(PIFAs)。KHT和hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3))。这两种脂肪酸在很小量的情况下就可以诱发对多种化疗药的抵抗。有趣的是，阻断参与合成这两个脂肪酸的核心酶，就可以阻止MSC诱发的耐药性。我们的结果显示，MSC是化疗耐药性的很强的调节者，MSC是提高化疗效能的靶标。, G* k; o/ w+ W( Q0 V
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阅读体会：1.这篇文章主要讲MSC可以诱发肿瘤化疗耐药，并找出了两个不饱和脂肪酸，这两种脂类只有在使用铂类化疗药时才会产生。考虑到铂类在化疗使用的广泛性，研究这个问题很重要啊，呵呵: O2 i; @7 R: e: t4 B1 c
2. 只有铂类才会诱导MSC分泌脂肪酸导致耐药，其他化疗药几乎不会引发，因而，文章的结果显示，MSC只对铂类有耐药性，对紫杉醇，5-氟尿嘧啶，等等基本不会引发耐药性。值得我们思考。3 R) i. M' t+ V- R# p! _' O1 @
3.该文寻找两个不饱和脂肪酸可是真正下了大工夫。先按分子量分，再按极性分，再运用化学分析的方法找到俩。。。) q/ x) \; f) o4 | y% _
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4.上一篇文献分享中 讲MSC是CAF的来源，这一篇文章讲MSC引发肿瘤耐药，进一步证明MSC是肿瘤的帮凶啊，应用在临床，务必要考虑其安全性！！！ ) d) p4 i6 C6 J) y0 r0 X, p9 h& {1 I2 K1 v b
望版主多加包包~~/ _/ v$ W* l- l- V' b1 Z7 |* ] 作者: 懵懂干细胞 时间: 2012-3-13 08:42
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