Evidence map›Paper›PMID 31922633›Full record

ArticleCancer science2020

Dual antivascular function of human fibulin-3 variant, a potential new drug discovery strategy for glioblastoma.

Chao Ke, Jun-Ran Luo, Zi-Wen Cen, Yanyan Li, Hai-Ping Cai, Jing Wang, Fu-Rong Chen, Eric R Siegel, Kody N Le, Jesica R Winokan and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 43% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Chao KeDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Jun-Ran LuoDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Zi-Wen CenDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yanyan LiNeurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Hai-Ping CaiDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Jing WangDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.ORCID https://orcid.org/0000-0002-0165-7237
Fu-Rong ChenDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Eric R SiegelDepartment of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Kody N LeDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
Jesica R WinokanDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
Grace J GibsonDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
Asia E McSwainDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
Kambiz AfrasiabiDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
Mark E LinskeyDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.
You-Xin ZhouNeurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.
Zhong-Ping ChenDepartment of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, China.
Yi-Hong ZhouDepartment of Neurological Surgery, Brain Tumor Research Laboratory, University of California, Irvine, CA, USA.ORCID https://orcid.org/0000-0002-8529-1032
University of California, Irvine · USSun Yat-sen University · CNSoochow University · CNUniversity of Arkansas for Medical Sciences · US

Funding

Guangzhou Science Technology Project 201508020125Musella Foundation For Brain Tumor Research and InformationScience and Technology Planning Project of Guangdong Province 2016A020213004The National Basic Research Program of China 2015CB755505The National Natural Science Foundation of China 81372685The National Natural Science Foundation of China 81572475The National Natural Science Foundation of China 81672484
6 · The paper itself

Abstract

The ECM protein EFEMP1 (fibulin-3) is associated with all types of solid tumor through its cell context-dependent dual function. A variant of fibulin-3 was engineered by truncation and mutation to alleviate its oncogenic function, specifically the proinvasive role in glioblastoma multiforme (GBM) cells at stem-like state. ZR30 is an in vitro synthesized 39-kDa protein of human fibulin-3 variant. It has a therapeutic effect in intracranial xenograft models of human GBM, through suppression of epidermal growth factor receptor/AKT and NOTCH1/AKT signaling in GBM cells and extracellular MMP2 activation. Glioblastoma multiforme is highly vascular, with leaky blood vessels formed by tumor cells expressing endothelial cell markers, including CD31. Here we studied GBM intracranial xenografts, 2 weeks after intratumoral injection of ZR30 or PBS, by CD31 immunohistochemistry. We found a 70% reduction of blood vessel density in ZR30-treated xenografts compared with that of PBS-treated ones. Matrigel plug assays showed the effect of ZR30 on suppressing angiogenesis. We further studied the effect of ZR30 on genes involved in endothelial transdifferentiation (ETD), in 7 primary cultures derived from 3 GBMs under different culture conditions. Two GBM cultures formed mesh structures with upregulation of ETD genes shortly after culture in Matrigel Matrix, and ZR30 suppressed both. ZR30 also downregulated ETD genes in two GBM cultures with high expression of these genes. In conclusion, multifaceted tumor suppression effects of human fibulin-3 variant include both suppression of angiogenesis and vasculogenic mimicry in GBM.

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorCell ProliferationDown-RegulationDrug DiscoveryEndothelial CellsErbB ReceptorsExtracellular Matrix ProteinsFemaleGene ExpressionGlioblastomaHumansMiceMice, Inbred BALB CMice, NudeEFEMP1 protein, humanErbB ReceptorsExtracellular Matrix Proteinsextracellular compartmentmalignant gliomanovel cancer therapeuticsyngeneic primary culturevasculogenic mimicry

Identifiers

PMID31922633
PMCPMC7060460
OpenAlexW2998930586

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.