Trends in Molecular Medicine:脂肪组织中这种蛋白会促进乳腺癌发展!

2020-04-15 竹子 转化医学网

导言:众所周知,较高的体内脂肪会增加患乳腺癌以及其他癌症的风险。詹姆斯·格雷厄姆·布朗癌症中心的研究人员发现,有13种癌症都与肥胖有关,而不仅仅是乳腺癌。

导言:众所周知,较高的体内脂肪会增加患乳腺癌以及其他癌症的风险。詹姆斯·格雷厄姆·布朗癌症中心的研究人员发现,有13种癌症都与肥胖有关,而不仅仅是乳腺癌。那么,脂肪组织中是否存在着某种物质在癌症(尤其是乳腺癌)与脂肪细胞之间起关键作用呢?

近日,詹姆斯·格雷厄姆·布朗癌症中心副教授,路易斯维尔大学(UofL)微生物、免疫学和健康学系李冰(Bing Li)博士发表了一篇文章。根据他正在进行的研究,提出了一种独特的理论,即脂肪组织中表达的脂肪酸结合蛋白(FABP4)可以促进乳腺癌肿瘤的生长。李在上周在线出版的细胞出版社杂志《分子医学趋势》的邀请论坛上分享了此论点。

早先就有研究探讨了膜突蛋白促进乳腺癌细胞侵袭转移机制,后又有研究从膜周边蛋白FABP4切入研究,表明其可以促进乳腺癌细胞的侵袭转移,机制可能是促进乳腺癌细胞IL-33的分泌有关。FABP4是脂肪酸结合蛋白家族的一员,能够结合多种疏水性化合物,例如长链脂肪酸、多种环氧化酶和脂肪氧化产物,同时参与其代谢和信号转导过程,并在糖尿病、肥胖和脂代谢紊乱等疾病的形成中发挥着关键作用。

在过去的五年中,李一直进行着由美国国家癌症研究所资助的研究,这使他认识到脂肪组织中表达的蛋白质的活性与乳腺癌发展的增加之间存在联系。他发现,脂肪酸结合蛋白家族,尤其是FABP4,在肥胖与癌症(尤其是乳腺癌)的关联中起着至关重要的作用。FABP4负责潜在的分子机制,促进跟肥胖相关的乳腺癌的发展。

人体中的脂肪组织在脂肪细胞内产生FABP4,在脂肪细胞中加工并分布不溶于水的长链脂肪酸。在正常情况下,一定量的FABP4进入血液。但是,随着脂肪组织积累量增加,更多的FABP4分泌进入循环系统。一个人变胖时,这种蛋白质会更多地分泌到循环系统中。通常这些分子在细胞内,但是当人们变胖时,这些分子在细胞外。

这项研究提供了FABP4刺激乳腺癌肿瘤生长的两种方式。首先,在细胞内,FABP4在某些与肿瘤相关的巨噬细胞中增加,这些巨噬细胞在肿瘤中积累以促进肿瘤生长。研究还显示,当FABP4被抑制时,即使脂肪组织残留,在动物模型中肿瘤的生长也会减少。其次,当肥胖中脂肪细胞外循环的FABP4水平升高时,该蛋白通过与乳腺癌细胞直接相互作用而促进乳腺癌的发展。在动物研究中,FAFA4受控制的肥胖动物的乳腺肿瘤发育和生长减少。

血液中的FABP4似乎以多种机制起作用,以促进肿瘤成分与脂肪细胞之间的相互作用,从而促进癌症的发展。

此外,研究小组最近在《癌症研究》上发表了研究结果,表明不同类型的高脂饮食对肿瘤的发展有不同的影响。高脂饮食的可可脂或鱼油都会导致肥胖。但是,可可脂饮食会增加乳腺肿瘤的生长,而鱼油饮食则不会。这项研究不仅证实了FABP4在与肥胖相关的癌症中的关键作用,而且揭示了一个道理:并非所有的肥胖都会促进肿瘤的发展。

研究人员相信,理解FABP4在巨噬细胞内和循环中如何运作,可以为预防某些乳腺癌的发展提供机会。它还可能促进研究人员开发以药物或特异性抗体靶向FABP4的治疗方法。这可能是一个非常有效的策略,还能治疗其他与肥胖相关的癌症。

原始出处:

Jun Zeng, Edward R. Sauter, Bing Li. FABP4: A New Player in Obesity-Associated Breast Cancer. Trends in Molecular Medicine April 07, 2020

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    2021-03-02 kalseyzl
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    2021-02-25 freve
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    2020-04-19 jeanqiuqiu
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    2020-04-17 智慧医人

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