Evidence map›Paper›PMID 39163136›Full record

ArticleJCI insight2024

Endothelial cell-specific LAT1 ablation normalizes tumor vasculature.

Jun-Ichi Suehiro, Toru Kimura, Toshiyuki Fukutomi, Hisamichi Naito, Yasuharu Kanki, Youichiro Wada, Yoshiaki Kubota, Nobuyuki Takakura, Hiroyuki Sakurai

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2024. 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
–field-weighted citation impact
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.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Multi-threshold volumetricNeuro-oncology advances
    Article
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

9 authors.

Jun-Ichi SuehiroDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Toru KimuraDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Toshiyuki FukutomiDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
Hisamichi NaitoDepartment of Vascular Physiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
Yasuharu KankiLaboratory of Clinical Examination and Sports Medicine, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Youichiro WadaIsotope Science Center, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Yoshiaki KubotaDepartment of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Nobuyuki TakakuraDepartment of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
Hiroyuki SakuraiDepartment of Pharmacology and Toxicology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Some endothelial cells in the tumor vasculature express a system L amino acid transporter, LAT1. To elucidate the role of LAT1 in tumor-related endothelial cells, tumor cells were injected into endothelial cell-specific LAT1 conditional knockout mice (Slc7a5flox/flox; Cdh5-Cre-ERT2), and we found that the shape of the tumor vasculature was normalized and the size and numbers of lung metastasis was reduced. TNF-α-induced expression of VCAM1 and E-selectin at the surface of HUVEC, both of which are responsible for enhanced monocyte attachment and premetastatic niche formation, was reduced in the presence of LAT1 inhibitor, nanvuranlat. Deprivation of tryptophan, a LAT1 substrate, mimicked LAT1 inhibition, which led to activation of MEK1/2-ERK1/2 pathway and subsequent cystathionine γ lyase (CTH) induction. Increased production of hydrogen sulfide (H2S) by CTH was at least partially responsible for tumor vascular normalization, leading to decreased leakiness and enhanced delivery of chemotherapeutic agents to the tumor.

Indexed as

Large Neutral Amino Acid-Transporter 1Mice, KnockoutAnimalsCell Line, TumorEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsLung NeoplasmsMiceNeovascularization, PathologicLarge Neutral Amino Acid-Transporter 1SLC7A5 protein, humanAmino acid metabolismAngiogenesisEndothelial cellsTransportVascular biology

Identifiers

PMID39163136
PMCPMC11457854

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Registered trials

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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.