Nature:胰腺癌“损人利己”机制或成治疗新靶点

2016-08-17 佚名 药明康德

胰腺癌是一种具有高度异质性的恶性肿瘤,是最为致命的癌症类型之一,五年期生存率不到5%。由于不易被早期诊断,有85%以上的胰腺癌患者都是在晚期才被确诊的,而这时已经无药可治了。胰腺癌的高侵袭性与其肿瘤的组成有关:胰腺癌肿瘤含有丰富的间质而血管较少,其间质成份通常占肿瘤体积的近90%,且与癌细胞之间保持着密切的信号联系,对癌症的发展十分关键。另一方面,正因为这样的特点,胰腺癌细胞要想生存下来,就必需在

胰腺癌是一种具有高度异质性的恶性肿瘤,是最为致命的癌症类型之一,五年期生存率不到5%。由于不易被早期诊断,有85%以上的胰腺癌患者都是在晚期才被确诊的,而这时已经无药可治了。胰腺癌的高侵袭性与其肿瘤的组成有关:胰腺癌肿瘤含有丰富的间质而血管较少,其间质成份通常占肿瘤体积的近90%,且与癌细胞之间保持着密切的信号联系,对癌症的发展十分关键。另一方面,正因为这样的特点,胰腺癌细胞要想生存下来,就必需在血液供应较少的情况下获取足够的养分。那么,胰腺癌细胞有着什么样的生存“秘笈”呢?

最近,来自哈佛大学和密歇根大学等机构的科学家们给出了答案。他们发现,胰腺癌细胞之所以能如此生存下去,是因为它们一直在干着“损人利已”的勾当——通过发送信息胰腺中的星状细胞(stellate cell)“上当”,使后者分解自己的细胞组分,然后供给癌细胞给养。这一成果发表在最近的《Nature》期刊上。

▲星状细胞向胰腺癌细胞输送营养(图片来源:《自然》)

原来,星状细胞在被胰腺癌细胞“误导”后,会启动自噬——这一本来通过溶酶体以回收细胞自身受损或衰老组分以供再利用的过程,而由此分解所得的氨基酸即被分泌的细胞外。这时,胰腺癌细胞便开始“大快朵颐”其中的丙氨酸和天冬氨酸这两种非必需氨基酸,供自己使用。其中,丙氨酸在经转氨酶作用会转化为丙酮酸,从而进入三羧酸(TCA)循环,为癌细胞提供能量以及合成其他所需养分。就这样,胰腺癌细胞的线粒体得以高速运转,以满足其生存和扩增的需求。

不过,胰腺癌细胞的这一生存伎俩有时也可成为“命门”。当研究人员通过基因技术阻断了小鼠体内星状细胞的自噬过程后,胰腺癌肿瘤的生长便被明显抑制住了。

▲Alec Kimmelman教授(图片来源:哈佛大学官网)

“我们的研究表明,胰腺癌细胞有着一种不同寻常的能量代谢形式,而且采取了比很多其他类型癌细胞更为高效的能量获取方式,”文章的通讯作者哈佛大学的Alec Kimmelman教授说道:“它揭示了肿瘤与星状细胞之间的一种全新的互动方式,这也许能为胰腺癌疗法的研发提供新思路,即干扰胰腺癌细胞的这种极具灵活性的代谢方式。”

参考资料:

[1] Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion

[2] Pancreatic cancer cells find unique fuel sources to keep from starving

[3] Pancreatic cancer stromal biology and therapy

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    2017-04-14 仁心济世
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    2016-10-26 WEIXINdbae2e30

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content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-09-18 ylzr123

    赞了!深度好文,深入学习。

    0

  4. 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content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-25 clivegranger

    除星状细胞外,其他细胞估计也行。

    0

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content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-20 136****0753赵

    值得学习

    0

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content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1881267, encodeId=8e0d188126e3c, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=仁心济世, createdTime=Fri Apr 14 00:32:00 CST 2017, time=2017-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=151351, encodeId=f96015135168, content=学习了,赞一个, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8ae1734613, createdName=WEIXINdbae2e30, createdTime=Wed Oct 26 13:58:21 CST 2016, time=2016-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=130572, encodeId=b0481305e2e2, content=赞了!深度好文,深入学习。, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun Sep 18 22:18:00 CST 2016, time=2016-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=103587, encodeId=b58610358e3a, content=除星状细胞外,其他细胞估计也行。, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=724c1678182, createdName=clivegranger, createdTime=Thu Aug 25 16:11:00 CST 2016, time=2016-08-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101536, encodeId=3f0e1015360c, content=值得学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLMzGpMQ8w4I7FpiblCXNcmI6O7TDINutbaicEUpoYFR1rWqn3kTbulfMhT0iaPFurLz2ddEcWe3BiciaQ/0, createdBy=5f6e1724878, createdName=136****0753赵, createdTime=Sat Aug 20 15:24:00 CST 2016, time=2016-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1517355, encodeId=1155151e35575, content=<a href='/topic/show?id=817b64646b3' target=_blank style='color:#2F92EE;'>#治疗新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64646, encryptionId=817b64646b3, topicName=治疗新靶点)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=251911073486, createdName=12498f1em11(暂无昵称), createdTime=Fri Aug 19 11:32:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1288177, encodeId=7c9e12881e708, content=<a href='/topic/show?id=f10658e342d' target=_blank style='color:#2F92EE;'>#新靶点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58734, encryptionId=f10658e342d, topicName=新靶点)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acc3210, createdName=lsndxfj, createdTime=Fri Aug 19 11:32:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100736, encodeId=b1ba100e3662, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100732, encodeId=b155100e32da, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100734, encodeId=0e5b100e348e, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-19 lsndxfj
  8. 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content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-19 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

    0

  9. 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topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100732, encodeId=b155100e32da, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100734, encodeId=0e5b100e348e, content=学习了,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Fri Aug 19 08:17:00 CST 2016, time=2016-08-19, status=1, ipAttribution=)]
    2016-08-19 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

    0

  10. 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    2016-08-19 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!

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