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Sökning: WFRF:(Zhang Xin) > (2020-2024) > Wnt signaling regul...

Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma

Xie, Yuan (författare)
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.
He, Liqun (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
Zhang, Yanyu (författare)
Fourth Mil Med Univ, Dept Neurosurg, Xijing Hosp, Xian 710032, Peoples R China.
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Huang, Hua, 1986- (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
Yang, Fan, Professor (författare)
Uppsala 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.
Chao, Min (författare)
Fourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, 569 Xinsi Rd, Xian 710038, Peoples R China.
Cao, Haiyan (författare)
Fourth Mil Med Univ, Dept Neurosurg, Tangdu Hosp, 569 Xinsi Rd, Xian 710038, Peoples R China.
Wang, Jianhao (författare)
Uppsala 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.
Li, Yaling (författare)
Xian Fourth Hosp, Dept Obstet & Gynaecol, Xian Peoples Hosp, Xian 710005, Peoples R China.
Zhang, Lingxue (författare)
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.
Xin, Lele (författare)
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.
Xiao, Bing (författare)
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.
Shi, Xinxin (författare)
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.
Zhang, Xue (författare)
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.
Tang, Jiefu (författare)
Hunan Univ Med, Trauma Ctr, Affiliated Hosp, Huaihua 418000, Peoples R China.
Uhrbom, Lene (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi och neurodegeneration
Dimberg, Anna (författare)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi
Wang, Liang (författare)
Fourth 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.
Zhang, Lei (författare)
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.;Shaanxi Normal Univ, Coll Life Sci, Xian 710119, Peoples R China.
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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)
2023-01-02
2023
Engelska.
Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:6, s. 1073-1084
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

blood-brain barrier
drug delivery
endothelial cell
glioblastoma
Wnt signaling

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