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Stem cells:PGD2/PTGDR2信号可抑制胃癌细胞进行自我更新,为控制胃癌进展提供新的思路

2018-04-02 MedSci MedSci原创

已知前列腺素D2(PGD2)对胃癌(GC)具有抗肿瘤作用已有十余年。但是,PGD2's对GC生长的控制机制尚未明确。癌症干细胞(CSCs)与肿瘤新生血管形成、侵袭性和治疗耐受性相关。近期研究人员发现PGD2与其受体(PTGDR2)之间的信号,在体外可抑制GC细胞的自我更新,在体内可抑制肿瘤增长转移。GC组织中PGD2合成酶(L-PTGDS)和PTGDR2表达水平明显低于邻近正常组织,并与患者预后相

已知前列腺素D2(PGD2)对胃癌(GC)具有抗肿瘤作用已有十余年。但是,PGD2's对GC生长的控制机制尚未明确。癌症干细胞(CSCs)与肿瘤新生血管形成、侵袭性和治疗耐受性相关。

近期研究人员发现PGD2与其受体(PTGDR2)之间的信号,在体外可抑制GC细胞的自我更新,在体内可抑制肿瘤增长转移。GC组织中PGD2合成酶(L-PTGDS)和PTGDR2表达水平明显低于邻近正常组织,并与患者预后相关。在GC组织中,L-PTGDS和PTGDR2的表达水平与GC-CSC标志物Sall4和Lgr5呈负相关。

敲低CSC样细胞的L-PTGDS和PTGDR2的表达,可导致CSC标志物表达上调、自我更新能力增强。直接刺激PGD2和过表达L-PTGDS可导致相反的效应。此外,PGD2可抑制肿瘤生长、皮下肿瘤模型的肿瘤发生率,还可抑制腹膜转移模型的肝和肠系膜癌转移。在活体中干扰PTGDR2表达则表现为上述相反的效应。

机制研究表明PGD2抑制STAT3磷酸化以及核表达。深入研究提示诱导STAT2磷酸化(Thr705)位点突变后,可丧失PGD2对CSC标志物表达的抑制作用。

简而言之,本研究揭示PGD2/PTGDR2信号对CSC自我更新具有调节作用,为我们控制GC进展提供新的思路。

原始出处:

Bin Zhang,et al,PGD2/PTGDR2 Signaling Restricts the Self‐Renewal and Tumorigenesis of Gastric Cancer.Stem cells. March 31,2018.https://doi.org/10.1002/stem.2821

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    2018-07-28 维他命
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time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302155, encodeId=50da30215550, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 02 22:53:20 CST 2018, time=2018-04-02, status=1, ipAttribution=)]
    2018-04-30 yhj-time
  4. 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time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302155, encodeId=50da30215550, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 02 22:53:20 CST 2018, time=2018-04-02, status=1, ipAttribution=)]
  5. 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time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302155, encodeId=50da30215550, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 02 22:53:20 CST 2018, time=2018-04-02, status=1, ipAttribution=)]
  6. 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time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302155, encodeId=50da30215550, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 02 22:53:20 CST 2018, time=2018-04-02, status=1, ipAttribution=)]
  7. 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channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86172, encryptionId=7287861e2ed, topicName=自我更新)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=764624964499, createdName=xsm926, createdTime=Wed Aug 22 20:45:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1252487, encodeId=33ad125248e76, content=<a href='/topic/show?id=3efee1519b2' target=_blank style='color:#2F92EE;'>#癌细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71519, encryptionId=3efee1519b2, topicName=癌细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4cea26, createdName=yxch36, createdTime=Wed Apr 04 12:45:00 CST 2018, time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482114, encodeId=6e7214821142b, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Wed Apr 04 12:45:00 CST 2018, time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1614992, encodeId=2f3016149921e, content=<a href='/topic/show?id=d74a44e2e7' target=_blank style='color:#2F92EE;'>#cells#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4472, encryptionId=d74a44e2e7, topicName=cells)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=659819575782, createdName=124988c7m101暂无昵称, createdTime=Wed Apr 04 12:45:00 CST 2018, time=2018-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=302155, encodeId=50da30215550, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Mon Apr 02 22:53:20 CST 2018, time=2018-04-02, status=1, ipAttribution=)]
    2018-04-04 yxch36
  8. 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    2018-04-02 131****2916

    不错的文章值得推荐

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