Evidence map›Paper›PMID 40647457›Full record

ArticleCancers2025

Targeting DAMPs by Aspirin Inhibits Head and Neck Cancer Stem Cells and Stimulates Radio-Sensitization to Proton Therapy.

Tea Vasiljevic, Emilija Zapletal, Marko Tarle, Iva Bozicevic Mihalic, Sabrina Gouasmia, Georgios Provatas, Kristina Vukovic Djerfi, Danko Müller, Koraljka Hat, Ivica Luksic and 1 more

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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Tea VasiljevicLaboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.ORCID 0000-0001-7195-6219
Emilija ZapletalLaboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Marko TarleDepartment of Maxillofacial Surgery, Dubrava University Hospital, Gojko Šušak Avenue 6, 10000 Zagreb, Croatia.ORCID 0000-0002-4173-1278
Iva Bozicevic MihalicLaboratory for Ion Beam Interactions, Division of Experimental Physics, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.ORCID 0000-0002-0221-4024
Sabrina GouasmiaLaboratory for Ion Beam Interactions, Division of Experimental Physics, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Georgios ProvatasLaboratory for Ion Beam Interactions, Division of Experimental Physics, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Kristina Vukovic DjerfiLaboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.
Danko MüllerDepartment of Pathology and Cytology, Dubrava University Hospital, Avenija Gojka Šuška 6, 10000 Zagreb, Croatia.
Koraljka HatDepartment of Maxillofacial Surgery, Dubrava University Hospital, Gojko Šušak Avenue 6, 10000 Zagreb, Croatia.ORCID 0000-0002-7058-4123
Ivica LuksicDepartment of Maxillofacial Surgery, Dubrava University Hospital, Gojko Šušak Avenue 6, 10000 Zagreb, Croatia.ORCID 0000-0002-9138-2037
Tanja Matijevic GlavanLaboratory for Personalized Medicine, Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb, Croatia.ORCID 0000-0002-1487-6164

Funding

Central European Research Infrastructure ConsortiumCroatian Science Foundation IP-2020-02-4225Croatian Science Foundation Young Researchers' career development project- training of doctoral studentsInternational Atomic Energy Agency CRP project F11024
6 · The paper itself

Abstract

backgroundCancer stem cells (CSCs) are a subpopulation of cancer cells known for their self-renewal capacity, tumorigenicity, and resistance to treatment. Toll-like receptor 3 (TLR3) plays a complex role in cancer, exhibiting both pro-apoptotic and pro-tumorigenic effects. This study investigates the pro-tumorigenic role of TLR3, specifically its impact on CSCs in head and neck cancer.

methodsWe have investigated Detroit 562, FaDu and SQ20B cell lines, the latter being stably transfected with a plasmid containing inducible shRNA for TLR3, by cultivating them to form tumor spheres in order to study CSCs.

resultsOur findings demonstrate that TLR3 activation promotes stemness in head and neck cancer cell lines. This is evidenced by increased tumor sphere formation, promotion of epithelial-to-mesenchymal transition (EMT), upregulated stemness gene expression, and elevated aldehyde dehydrogenase (ALDH) activity. Conditional TLR3 knockdown abolished tumor sphere formation, confirming its important role. Furthermore, TLR3 activation triggers the secretion of damage-associated molecular patterns (DAMPs) into the tumor microenvironment, leading to increased cancer cell migration. This was inhibited by DAMP inhibitors. In patient tissue samples, we observed co-localization of TLR3 with stemness markers CD133 and ALDH1, as well as with heat shock protein 70 (HSP70) and receptor for advanced glycation end products (RAGE). We then explored potential CSC-targeted therapies, initially combining the apoptosis inducer poly (I:C) with DAMP inhibitors and γ-irradiation. While this combination proved effective in adherent cells, it failed to eliminate tumor spheres. Nevertheless, we discovered that proton radiotherapy, particularly when combined with aspirin (HMGB1 inhibitor) and poly (I:C), effectively eliminates CSCs.

conclusionsThis novel combination holds promise for the development of new therapeutic strategies for head and neck cancers, particularly given the promising results of proton therapy in treating this disease.

Indexed as

aspirincancer stem cells Toll-like receptor 3 (TLR3)damage-associated molecular patterns (DAMPs)migrationproton irradiationγ-irradiation

Identifiers

PMID40647457
PMCPMC12249109

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.