Evidence map›Paper›PMID 35135586›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

cPLA2 blockade attenuates S100A7-mediated breast tumorigenicity by inhibiting the immunosuppressive tumor microenvironment.

Sanjay Mishra, Manish Charan, Rajni Kant Shukla, Pranay Agarwal, Swati Misri, Ajeet K Verma, Dinesh K Ahirwar, Jalal Siddiqui, Kirti Kaul, Neety Sahu and 7 more

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

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Elucidating the role of S100A10 in CD8Cell death & disease · 2024
    Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

17 authors at 2 institutions in 1 country.

Sanjay Mishra *Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA. sanjay.mishra@osumc.edu.
Manish Charan *Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Rajni Kant ShuklaDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Pranay AgarwalDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, 94305, USA.
Swati MisriDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Ajeet K VermaDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Dinesh K AhirwarDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Jalal SiddiquiComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Kirti KaulDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Neety SahuDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, 94305, USA.
Kunj VyasDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Ayush Arpit GargDepartment of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, 43210, USA.
Anum KhanSchool of Medicine, Cell Science Imaging Facility, Stanford University, Stanford, CA, 94305, USA.
Wayne O MilesComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Jonathan W SongComprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Nidhi BhutaniDepartment of Orthopaedic Surgery, Stanford University, Stanford, CA, 94305, USA.
Ramesh K GanjuDepartment of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA. ramesh.ganju@osumc.edu.
The Ohio State University · USStanford University · US

Funding

Establishing a Single-Cell Proteomic Atlas for Normal and Osteoarthritic Articular CartilageR01AR077530 · NIAMS · STANFORD UNIVERSITY · PI BHUTANI, NIDHI · 2021 to 2025
$2.6M
Role of Slit in CXCR4-Mediated Breast Cancer MetastasisR01CA109527 · NCI · OHIO STATE UNIVERSITY · PI GANJU, RAMESH K. · 2005 to 2019
$2.6M
The translation regulation of pro-apoptotic genesR01CA251753 · NCI · OHIO STATE UNIVERSITY · PI MILES, WAYNE · 2020 to 2024
$2.0M
Role of S100A7 in breast cancer progression and metastasisR01CA153490 · NCI · OHIO STATE UNIVERSITY · PI GANJU, RAMESH K. · 2011 to 2014
$1.2M
NCI NIH HHS R01 CA109527NCI NIH HHS R01 CA153490NCI NIH HHS R01 CA251753NIAMS NIH HHS R01 AR077530NIH HHS CA109527NIH HHS CA153490U.S. Department of Defense W81XWH1910088
6 · The paper itself

Abstract

backgroundMolecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear.

methodsHuman breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells.

resultsIn this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4

conclusionsOur study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorCell ProliferationDisease Models, AnimalFemaleHumansMicePhospholipases A2, CytosolicS100 Calcium Binding Protein A7Tumor MicroenvironmentPhospholipases A2, CytosolicS100A7 protein, humanS100 Calcium Binding Protein A7Breast cancercPLA2MetastasisPGE2S100A7Tumor microenvironment

Identifiers

PMID35135586
PMCPMC8822829
OpenAlexW4225484942

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.