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Wnt signaling regul...
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Xie, YuanShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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2023-01-02
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Oxford University Press,2023
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-512762
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-512762URI
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https://doi.org/10.1093/neuonc/noac288DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Background: Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.Methods: Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.Results: We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.Conclusions: These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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He, LiqunUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi(Swepub:uu)liqhe592
(författare)
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Zhang, YanyuFourth Mil Med Univ, Dept Neurosurg, Xijing Hosp, Xian 710032, Peoples R China.
(författare)
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Huang, Hua,1986-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi(Swepub:uu)huahu114
(författare)
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Yang, Fan,ProfessorUppsala universitet,Vaskulärbiologi,Science for Life Laboratory, SciLifeLab,Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin Neurol Inst, Key Lab Postneuroinjury Neurorepair & Regenerat Ce, Tianjin 300052, Peoples R China.(Swepub:uu)fanya562
(författare)
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Chao, MinFourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, 569 Xinsi Rd, Xian 710038, Peoples R China.
(författare)
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Cao, HaiyanFourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, 569 Xinsi Rd, Xian 710038, Peoples R China.
(författare)
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Wang, JianhaoUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Tianjin Med Univ Gen Hosp, Dept Neurosurg, Tianjin Neurol Inst, Key Lab Postneuroinjury Neurorepair & Regenerat Ce, Tianjin 300052, Peoples R China.
(författare)
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Li, YalingXian Fourth Hosp, Dept Obstet & Gynaecol, Xian Peoples Hosp, Xian 710005, Peoples R China.
(författare)
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Zhang, LingxueShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
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Xin, LeleShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
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Xiao, BingShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
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Shi, XinxinShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
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Zhang, XueShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.
(författare)
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Tang, JiefuHunan Univ Med, Trauma Ctr, Affiliated Hosp, Huaihua 418000, Peoples R China.
(författare)
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Uhrbom, LeneUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi och neurodegeneration(Swepub:uu)leneuhrb
(författare)
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Dimberg, AnnaUppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi(Swepub:uu)annadimb
(författare)
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Wang, LiangFourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, 569 Xinsi Rd, Xian 710038, Peoples R China.;Fourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, Xian, Peoples R China.
(författare)
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Zhang, LeiShaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.;Shaanxi Normal Univ, Coll Life Sci, Xian 710119, Peoples R China.
(författare)
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Shaanxi Normal Univ, China Sweden Int Joint Res Ctr Brain Dis, Key Lab, Minist Educ Med Plant Resource & Nat Pharmaceut Ch, Xian 710119, Peoples R China.Science for Life Laboratory, SciLifeLab
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Neuro-Oncology: Oxford University Press25:6, s. 1073-10841522-85171523-5866
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Till lärosätets databas
- Av författaren/redakt...
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Xie, Yuan
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He, Liqun
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Zhang, Yanyu
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Huang, Hua, 1986 ...
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Yang, Fan, Profe ...
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Chao, Min
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visa fler...
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Cao, Haiyan
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Wang, Jianhao
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Li, Yaling
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Zhang, Lingxue
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Xin, Lele
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Xiao, Bing
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Shi, Xinxin
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Zhang, Xue
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Tang, Jiefu
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Uhrbom, Lene
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Dimberg, Anna
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Wang, Liang
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Zhang, Lei
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visa färre...
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MEDICIN OCH HÄLS ...
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och Cell och molekyl ...
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och Klinisk medicin
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och Cancer och onkol ...
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Neuro-Oncology
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Uppsala universitet