ArticleBreast cancer research : BCR2025
Semaphorin-7A promotes macrophage-mediated mammary epithelial and ductal carcinoma in situ invasion.
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 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Postpartum breast cancer as a distinct oncologic entity: linking physiological tissue remodelling to tumor biology and clinical translation.Breast cancer research : BCR · 2026Review
- SOX9 and SEMA7A regulate cell plasticity in the postpartum mammary gland with implications for breast cancer.bioRxiv : the preprint server for biology · 2026Article
Corrections and comments
- Update of
Authors and funding
5 authors.
Funding
Abstract
backgroundDuctal carcinoma in situ (DCIS) accounts for 20–30% of all breast cancer diagnoses. Considered stage 0, DCIS is contained in the ducts by the myoepithelium that surround the luminal cells in the mammary gland. DCIS can progress to invasive ductal carcinoma (IDC) if the tumor cells break through the myoepithelium and invade the surrounding breast tissue. While 30–50% of DCIS tumors will progress to IDC, a majority will remain in a DCIS-like state. The mechanisms that drive this progression are not completely understood. There is currently no clinically recognized biomarker for predicting risk of DCIS progression. Therefore, all DCIS tumors are treated with standard of care, resulting in overtreatment. We have previously identified independent roles for semaphorin-7A(SEMA7A) and collagen in promoting DCIS progression to IDC.
methodsTo investigate the relationship between SEMA7A and collagen remodeling in the mammary gland, we utilized patient tissues and mouse models of normal development and DCIS progression as well as a novel SEMA7A-blocking antibody.
resultsWe show that SEMA7A increases in patient samples of DCIS compared to matched normal tissues and in IDC compared to matched DCIS and normal tissues. This increase was correlated with the presence of CD68 + macrophages. Using puberty in the mammary gland as a model for normal epithelial invasion facilitated by macrophages, we show SEMA7A knockout mice exhibit delayed ductal elongation as well as decreased macrophages. Additionally, our SEMA7A-blocking antibody in a mouse model of DCIS decreased invasive tumor phenotypes and decreased organized collagen around the tumor. The invasive tumors had increased collagen and macrophage influx in the tumor. Finally, we show that SEMA7A activates an AKT/GSK3β/β-catenin signaling pathway within macrophages to promote expression of pro-inflammatory cytokines and the matrix remodeling enzyme MMP9 to facilitate invasion.
conclusionsOur results demonstrate that SEMA7A regulates normal and transformed epithelial cell invasion through regulation of pro-invasive matrix remodeling via macrophages. Our studies also suggest that SEMA7A expression, macrophage phenotype, and collagen structure may be a predictor of risk for DCIS invasion. Thus, blocking SEMA7A may be a novel therapeutic strategy for high-risk DCIS patients to slow or prevent progression of disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.