Evidence map›Paper›PMID 36608459›Full record

ArticleOral oncology2023

Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma.

Prokopios P Argyris, Flávia Saavedra, Chris Malz, Ian A Stone, Yuping Wei, William S Boyle, Karen F Johnstone, Ali Khammanivong, Mark C Herzberg

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

Article in Oral oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

  1. RAPTOR Silencing Inhibits Head and Neck Squamous Cell Carcinoma Progression via Regulation of S100A8/A9 and Urokinase Plasminogen Activator.Medical science monitor : international medical journal of experimental and clinical research · 2026
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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

9 authors at 3 institutions in 1 country.

Prokopios P ArgyrisDepartment of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN, USA; Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN, USA; Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN, USA. Electronic address: argyr005@umn.edu.
Flávia SaavedraDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
Chris MalzDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
Ian A StoneDepartment of Immunology, Microbiology and Virology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA.
Yuping WeiDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
William S BoyleDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
Karen F JohnstoneDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA.
Ali KhammanivongMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, USA.
Mark C HerzbergDepartment of Diagnostic and Biological Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USA. Electronic address: mcherzb@umn.edu.
University of Minnesota · USHoward Hughes Medical Institute · USUniversity of Rochester · US

Funding

Minnesota Craniofacial Research Training ProgramT90DE022732 · NIDCR · UNIVERSITY OF MINNESOTA · PI MANSKY, KIM CARPENTER · 2012 to 2023
$4.9M
Minnesota Craniofacial Research Training ProgramR90DE023058 · NIDCR · UNIVERSITY OF MINNESOTA · PI MANSKY, KIM CARPENTER · 2012 to 2022
$1.2M
Augmenting Innate Immunity to Protect the Oral MucosaR01DE021206 · NIDCR · UNIVERSITY OF MINNESOTA · PI HERZBERG, MARK C · 2010 to 2013
$1.2M
A novel, two-armed autotherapy for mucosal infectious diseasesR21DE029337 · NIDCR · UNIVERSITY OF MINNESOTA · PI HERZBERG, MARK C · 2020 to 2021
$461k
NIDCR NIH HHS R01 DE021206NIDCR NIH HHS R21 DE029337NIDCR NIH HHS R90 DE023058NIDCR NIH HHS T90 DE022732
6 · The paper itself

Abstract

objectivesIn head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation. MATERIALS AND

methodsHuman HNSCC cases in TCGA were analyzed for relationships between S100A8/A9 and expression of apoptosis-related genes. Next, S100A8/A9-expressing and non-expressing carcinoma lines (two different lineages) were exposed to genotoxic agents and assessed for 53BP1 and γH2AX expression and percent of viable/dead cells. Finally, S100A8/A9-wild-type and S100A8/A9

resultsIn S100A8/A9-high HNSCC tumors, apoptosis-related caspase family member genes were upregulated, whereas genes limiting apoptosis were significantly downregulated based on TCGA analyses. After X-irradiation or camptothecin treatment, S100A8/A9-expressing carcinoma cells (i.e., TR146 and KB-S100A8/A9) showed significantly higher 53BP1 and γH2AX expression, DNA fragmentation, proportions of dead cells, and greater sensitivity to cisplatin than wild-type KB or TR146-S100A8/A9-KD cells. Interestingly, KB-S100A8/A9

conclusionsIn HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy.

Indexed as

CarcinomaHead and Neck NeoplasmsAnimalsApoptosisCalgranulin ACalgranulin BHumansLeukocyte L1 Antigen ComplexMiceMice, Inbred C57BLSquamous Cell Carcinoma of Head and NeckCalgranulin ACalgranulin BLeukocyte L1 Antigen ComplexS100A8 protein, humanS100a8 protein, mouse53BP1CalprotectinCisplatinDNA damageDouble-strand breaksHead and neck cancerHead and neck squamous cell carcinomaRadiationS100A8/A9γH2AX

Identifiers

PMID36608459
PMCPMC9877195
OpenAlexW4313593840

What OpenQuestion holds

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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 OpenQuestion graph.