Evidence map›Paper›PMID 41345673›Full record

ArticleBreast cancer research : BCR2025

Secreted frizzled-related protein 2 monoclonal antibody-mediated IFN-ϒ reprograms tumor-associated macrophages to suppress triple negative breast cancer.

Lillian Hsu, Julie Siegel, Patrick Nasarre, Nathaniel Oberholtzer, Rupak Mukherjee, Eleanor Hilliard, Paramita Chakraborty, Rachel A Burge, Elizabeth C O'Quinn, Olivia Sweatt and 6 more

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 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. 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

16 authors.

Lillian HsuDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Julie SiegelDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Patrick NasarreTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Nathaniel OberholtzerDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Rupak MukherjeeDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Eleanor HilliardDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Paramita ChakrabortyDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Rachel A BurgeTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Elizabeth C O'QuinnHollings Cancer Center Biorepository and Tissue Analysis Shared Resource, Medical University of South Carolina, Charleston, SC, 29425, USA.
Olivia SweattDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Mohamed Faisal KassirTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
G Aaron HobbsTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Michael OstrowskiTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Ann-Marie BroomeTherapeutics Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA.
Shikhar MehrotraDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA.
Nancy Klauber-DeMoreDepartment of Surgery, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, HO712J, Charleston, SC, 29425, USA. demore@musc.edu.

Funding

Translational Science Laboratory Shared ResourceP30CA138313 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI RAYMOND N. DUBOIS · 2009 to 2026
$42.7M
Congressionally Directed Medical Research Programs W81XWH-18-1-0007NCI NIH HHS P30 CA138313
6 · The paper itself

Abstract

purposeWe hypothesize that SFRP2 is a promising target for Triple Negative Breast Cancer (TNBC). EXPERIMENTAL

design1. Multiplex immunohistochemistry (IHC) was performed on human TNBC to identify SFRP2 localization in the tumor microenvironment. 2. Tumor associated macrophages (TAMs) were isolated from E0771.LMB breast tumors. TAMs were treated with hSFRP2 mAb (10 µM) or control (10 µM) for 1 h and analyzed by western blot and qRT-PCR for IFN-ϒ. 3 SFRP2 and IFN-ϒ mRNA expression levels were analyzed from the Cancer Genome Atlas (tCGA) for breast cancer patients using least squares-linear regression analysis. 4. PY8119 or E0771.LMB TNBC cells were injected i.v. into mice, and mice were treated with either IgG1 or hSFRP2 mAb every 3 days. Lung metastases were counted after 4 weeks and analyzed by IHC for M1/M2 ratio. 5. MDA-MB-231 TNBC cells were injected into the mammary fat pad, and when tumors were established, mice were treated with IGg1 or hSFRP2 mAb every 3 days i.v. for 79 days and tumor volumes were compared. 6. Wild-type (WT) MDA-MB-231 and doxorubicin-resistant MDA-MB-231 cells were treated with hSFRP2 mAb and apoptosis was compared.

results1) Multiplex IHC on human breast tumors showed that SFRP2 localized to tumor cells (87%), TAMs (90%), and tumor-infiltrating lymphocytes (TILs) (96%) in the microenvironment. 2) TAMs treated with hSFRP2 mAb had an increase in IFN-ϒ mRNA by 2.35 ± 0.08-fold (n = 3, p = 0.02) and protein levels by1.9-fold compared to control. 3). Analysis of 1075 breast cancer patients from TCGA database revealed a significant negative association between SFRP2 mRNA and IFN-ϒ expression (p < 0.0001). 4) hSFRP2 mAb reduced lung metastases in EO771.LMB (n = 15, p < 0.05) and PY8119 (n = 11, p < 0.05) mice with an increase the M1/M2 ratio in lungs (n = 3, p = 0.02). 5) hSFRP2 mAb inhibited MDA-MB-231 growth in vivo by 61% percent (n = 9, p < 0.001). 6) hSFRP2 mAb promoted apoptosis in doxorubicin-resistant cells (n = 6, p < 0.0001).

conclusionsSFRP2 localizes to tumor, TAMs and TILs in the tumor microenvironment and is negatively associated INF-ƴ in human tumors. hSFRP2 mAb reduces primary and metastatic TNBC growth, increases INF-ƴ from TAMS, boosts the M1/M2 ratio in lung metastases, and induces apoptosis in doxorubicin-resistant cells.

Indexed as

Antibodies, MonoclonalMembrane ProteinsTriple Negative Breast NeoplasmsTumor-Associated MacrophagesAnimalsApoptosisCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceSecreted Frizzled-Related ProteinsTumor MicroenvironmentXenograft Model Antitumor AssaysAntibodies, MonoclonalMembrane ProteinsSecreted Frizzled-Related ProteinsSFRP2 protein, humanApoptosisBiodistributionCD38Chemotherapy resistanceImmunotherapyM1M2T-cellsTumor microenvironmentWNT

Identifiers

PMID41345673
PMCPMC12679742

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.