Evidence map›Paper›PMID 39858106›Full record

ArticleCancers2025

Impact of Hyaluronic Acid on the Cutaneous T-Cell Lymphoma Microenvironment: A Novel Anti-Tumor Mechanism of Bexarotene.

Tetsuya Ikawa, Emi Yamazaki, Ryo Amagai, Yumi Kambayashi, Mana Sekine, Takuya Takahashi, Yoshihide Asano, Taku Fujimura

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

8 authors.

Tetsuya IkawaDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0000-0002-2753-9001
Emi YamazakiDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0000-0002-1189-3962
Ryo AmagaiDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0009-0008-3337-5657
Yumi KambayashiDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0000-0003-3866-5609
Mana SekineDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Takuya TakahashiDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0009-0008-0927-6616
Yoshihide AsanoDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0000-0001-5560-9778
Taku FujimuraDepartment of Dermatology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.ORCID 0000-0001-6809-5833

Funding

Minophagen Pharmaceutical Co. Ltd. not applicablethe Japan Society for the Promotion of Science 21K08318, 22K162750, 22K083990
6 · The paper itself

Abstract

backgroundCutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin's lymphoma that primarily affects the skin, rich in hyaluronic acid (HA). HA is a component of the extracellular matrix in the dermis and likely affects the development of CTCL, but the mechanism is poorly understood. Here we show that low-molecular-weight HA (LMWHA) possibly exacerbates CTCL, and bexarotene, already used in CTCL treatment, decreases HA production.

methodsWe conducted immunohistochemistry, qRT-PCR, immunoblotting, and HA quantification using both mouse and human specimens to evaluate the impact of HA on CTCL. Additionally, we assessed the effect of bexarotene, which is already used for CTCL treatment, on HA metabolism.

resultsHA expression was higher in patients' serum and skin sections than in healthy controls. HA extracted from the skin of mice inoculated with tumors showed an increase in LMWHA. LMWHA increased lymphoma cell proliferation in vitro and accelerated tumor formation in mice in vivo. LMWHA also created a favorable environment for tumor cells by affecting fibroblasts, vascular endothelial cells, and tumor-associated macrophages. Thus, increased levels of HA, mainly LMWHA, exacerbate CTCL progression by affecting tumor cells and their microenvironment. Bexarotene treatment reduced the amount of total HA in murine tumor-inoculated skin, as well as the supernatant of cultured normal human dermal fibroblasts (NHDFs) and HuT78 cells. Detailed in vitro analyses showed that bexarotene treatment decreased HA synthase (HAS)1 and HAS2 expression in NHDFs and HAS1 and HAS3, and CEMIP expression in HuT78 cells. Chromatin immunoprecipitation assays revealed that bexarotene reduced retinoid X receptor-α binding to the

conclusionsBexarotene potentially exerts its anti-tumor effect by reducing HA levels through decreased expression of HAS. These findings provide new insights into the process of CTCL development and additional insights regarding bexarotene treatment.

Indexed as

bexaroteneCTCLHAShigh-molecular-weight HAhyaluronic acid (HA)low-molecular-weight HA

Identifiers

PMID39858106
PMCPMC11764198

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.