Evidence map›Paper›PMID 36411463›Full record

ArticleJournal of biomedical science2022

Tumor-associated macrophages promote resistance of hepatocellular carcinoma cells against sorafenib by activating CXCR2 signaling.

Hao-Chen Wang, Lin-Ya Haung, Chih-Jung Wang, Ying-Jui Chao, Ya-Chin Hou, Chia-Jui Yen, Yan-Shen Shan

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

41 citing papers in PubMed, 63 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Hao-Chen WangInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35, Xiaodong Road, Tainan, 704017, Taiwan.
Lin-Ya HaungInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35, Xiaodong Road, Tainan, 704017, Taiwan.
Chih-Jung WangDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Shengli Road, Tainan, 704302, Taiwan.
Ying-Jui ChaoDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Shengli Road, Tainan, 704302, Taiwan.
Ya-Chin HouDepartment of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Shengli Road, Tainan, 704302, Taiwan.
Chia-Jui YenDepartment of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 138, Shengli Road, Tainan, 704302, Taiwan.
Yan-Shen ShanInstitute of Clinical Medicine, College of Medicine, National Cheng Kung University, No. 35, Xiaodong Road, Tainan, 704017, Taiwan. ysshan@mail.ncku.edu.tw.ORCID http://orcid.org/0000-0002-2457-5189
National Cheng Kung University Hospital · TWNational Cheng Kung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSorafenib (SOR) is the first line treatment for advanced hepatocellular carcinoma (HCC), but resistance develops frequently. Tumor-associated macrophages (TAMs) have been reported to affect the progression of HCC. We therefore aimed to study the role of TAMs in promoting SOR resistance.

methodsImmunofluorescence staining for the M2 marker CD204 and the cancer stem cell (CSC) markers CD44 and CD133 was performed in paired HCC and adjacent noncancerous tissues and HCC tissues stratified by response of SOR treatment. HCC/U937 coculture system and cytokines were used to induce M2 polarization for studying the effects of M2 TAMs on CSC properties and apoptotic death of HCC cells after SOR treatment.

resultsHigher expression of CD204, CD44, and CD133 was observed in patients with SOR nonresponse (SNR) than in those with SOR response (SR), suggesting that SNR is positively correlated to levels of CSCs and M2 TAMs. After coculture, M2 TAMs could increase the level of CSCs but decrease SOR-induced apoptosis. Incubation of HCC cells with coculture conditioned medium increased the formation of spheres that were resistant to SOR. Furthermore, CXCL1 and CXCL2 were found to be the potential paracrine factors released by M2 TAMs to upregulate SOR resistance in HCC cells. Treatment with CXCL1 and CXCL2 could increase HCC CSC activity but decrease SOR-induced apoptosis by affecting BCL-2 family gene expression. Using pharmacological inhibitors, CXCR2/ERK signaling was found to be critical to CXCL1- and CXCL2-mediated SOR resistance.

conclusionThis study identified CXCL1, CXCL2, and their downstream CXCR2/ERK signaling as potential therapeutic targets to overcome SOR resistance in HCC.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsHumansReceptors, Interleukin-8BSorafenibTumor-Associated MacrophagesReceptors, Interleukin-8BSorafenibCXCL1CXCL2CXCR2Hepatocellular carcinomaSorafenib resistanceTumor-associated macrophage

Identifiers

PMID36411463
PMCPMC9677647
OpenAlexW4309666716

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.