BMC Cancer:多倍体脂肪干细胞产生的胰岛素样生长因子1的增加促进了乳腺癌细胞的生长

2018-09-11 MedSci MedSci原创

脂肪组织干细胞(ASCs)因其成功用于再生疗法而受到深入研究。ASCs的缺点是其可以作为癌细胞的基质并帮助肿瘤进展。但是,ASCs在体外繁殖过程中经常发生遗传和表观遗传变化。在本研究中,我们描述了小鼠ASCs的多倍化以及伴随的长期培养中的表型、基因表达和功能变化。从C57BL / 6J小鼠的内脏脂肪中分离ASCs,并在体外培养。通过显微镜和流式细胞术跟踪表型变化。通过差异转录组分析确定基因表达变化

脂肪组织干细胞(ASCs)因其成功用于再生疗法而受到深入研究。ASCs的缺点是其可以作为癌细胞的基质并帮助肿瘤进展。但是,ASCs在体外繁殖过程中经常发生遗传和表观遗传变化。在本研究中,我们描述了小鼠ASCs的多倍化以及伴随的长期培养中的表型、基因表达和功能变化。

从C57BL / 6J小鼠的内脏脂肪中分离ASCs,并在体外培养。通过显微镜和流式细胞术跟踪表型变化。通过差异转录组分析确定基因表达变化,并通过蛋白质印迹探究蛋白质表达的变化。通过与4种T1鼠乳腺癌细胞共培养来检测ASCs的肿瘤生长促进作用。

传代5次后,ASCs的增殖减少,细胞进入衰老样状态,一部分细胞通过多倍化作用逃脱。得到的ASC系易受脂肪形成、成骨和软骨形成分化的影响,且干细胞标志物CD29和Sca-1的表达水平上调。具有正常和多倍体核型的ASC的差异转录组分析显示参与癌症、细胞生长和增殖调节的基因表达发生改变。我们验证了Klf4的表达增加和Nestin在蛋白质水平上的减少。多倍体ASCs提高胰岛素样生长因子1的产生使其在体外促进肿瘤生长方面更有效。

综上所述,该研究结果揭示了遗传背景改变的ASCs如何促进肿瘤进展。

原始出处:

Roberta Fajka-Boja, Annamária Marton, et al., Increased insulin-like growth factor 1 production by polyploid adipose stem cells promotes growth of breast cancer cells. BMC Cancer. 2018; 18: 872.

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    2019-03-23 baoya
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createdBy=0aa31415219, createdName=orangesking, createdTime=Tue Sep 11 21:49:00 CST 2018, time=2018-09-11, status=1, ipAttribution=)]
  5. 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target=_blank style='color:#2F92EE;'>#脂肪干细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84346, encryptionId=dd2884346fe, topicName=脂肪干细胞)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Sep 13 11:41:00 CST 2018, time=2018-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1518010, encodeId=9dec151801039, content=<a href='/topic/show?id=aa2269613cd' target=_blank style='color:#2F92EE;'>#生长因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69613, encryptionId=aa2269613cd, topicName=生长因子)], attachment=null, authenticateStatus=null, createdAvatar=null, 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createdBy=0aa31415219, createdName=orangesking, createdTime=Tue Sep 11 21:49:00 CST 2018, time=2018-09-11, status=1, ipAttribution=)]
    2018-09-13 yxch36
  6. 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  7. 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  8. 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  9. 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createdBy=0aa31415219, createdName=orangesking, createdTime=Tue Sep 11 21:49:00 CST 2018, time=2018-09-11, status=1, ipAttribution=)]
    2018-09-11 orangesking

    0