Modulatory function of cancer-associated fibroblasts in shaping macrophage polarisation and tumour invasion in luminal breast cancers.
5 affiliations
- 1Department of Electroradiology, Poznan University of Medical Sciences, Poznan, Poland.
- 2Doctoral School, Poznan University of Medical Sciences, Poznan, Poland.
- 3Radiobiology Laboratory, Department of Medical Physics, Greater Poland Cancer Center, Poznan, Poland.
- 4Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland.
- 5Breast Cancer Unit, Breast Surgical Oncology Department, Greater Poland Cancer Center, Poznan, Poland.
Abstract
Breast cancer (BC) remains a major cause of cancer-related mortality among women worldwide, with therapeutic resistance posing a significant challenge. The tumour microenvironment (TME), particularly the interplay between cancer-associated fibroblasts (CAFs) and macrophages, contributes to immune evasion, invasion, and drug resistance. Resveratrol (RV) is a pleiotropic compound with reported anticancer effects, but its influence on complex stromal interactions is poorly understood. A 3D multicellular spheroid model of luminal BC, incorporating CAFs, macrophages, and cancer cells, was employed to investigate how CAF-macrophage cross-talk modulates tumour behaviour and how RV affects these dynamics, using methods including flow cytometry, invasion assays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cancer-associated fibroblasts were functionally grouped into RV-restricted (rrCAFs) and RV-stimulated (rsCAFs) based on their transcriptional and phenotypic responses. rrCAFs downregulated pro-invasive genes and induced M1 macrophage polarisation following RV treatment, whereas rsCAFs retained high expression of extracellular matrix (ECM) remodelling and Notch pathway components, promoting an M2-like phenotype. rsCAF-containing spheroids exhibited the highest invasiveness and filopodia formation, supported by elevated IL-6, MCP-1, and CXCR4 expression, while RV only partially reduced invasion. These findings reveal heterogeneity in CAF responses and link the inflammatory CAF phenotype to reduced RV efficacy, underscoring the importance of CAF subtyping for predicting therapeutic outcomes. This work supports personalised, stroma-targeted strategies to overcome BC progression and resistance.
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BibTeX
@article{piwocka2026modulatory,
title = {{Modulatory function of cancer-associated fibroblasts in shaping macrophage polarisation and tumour invasion in luminal breast cancers.}},
author = {Oliwia Piwocka and Julia Kobojek and Piotr Nowaczyk and Igor Piotrowski and Katarzyna Kulcenty},
journal = {Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology},
year = {2026},
month = nov,
doi = {10.5603/rpor.115360},
url = {https://europepmc.org/article/MED/42997643},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Modulatory function of cancer-associated fibroblasts in shaping macrophage polarisation and tumour invasion in luminal breast cancers.
AU - Oliwia Piwocka
AU - Julia Kobojek
AU - Piotr Nowaczyk
AU - Igor Piotrowski
AU - Katarzyna Kulcenty
PY - 2026
DA - 2026/11/01
JO - Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology
DO - 10.5603/rpor.115360
UR - https://europepmc.org/article/MED/42997643
AB - Breast cancer (BC) remains a major cause of cancer-related mortality among women worldwide, with therapeutic resistance posing a significant challenge. The tumour microenvironment (TME), particularly the interplay between cancer-associated fibroblasts (CAFs) and macrophages, contributes to immune evasion, invasion, and drug resistance. Resveratrol (RV) is a pleiotropic compound with reported anticancer effects, but its influence on complex stromal interactions is poorly understood. A 3D multicellular spheroid model of luminal BC, incorporating CAFs, macrophages, and cancer cells, was employed to investigate how CAF-macrophage cross-talk modulates tumour behaviour and how RV affects these dynamics, using methods including flow cytometry, invasion assays and reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cancer-associated fibroblasts were functionally grouped into RV-restricted (rrCAFs) and RV-stimulated (rsCAFs) based on their transcriptional and phenotypic responses. rrCAFs downregulated pro-invasive genes and induced M1 macrophage polarisation following RV treatment, whereas rsCAFs retained high expression of extracellular matrix (ECM) remodelling and Notch pathway components, promoting an M2-like phenotype. rsCAF-containing spheroids exhibited the highest invasiveness and filopodia formation, supported by elevated IL-6, MCP-1, and CXCR4 expression, while RV only partially reduced invasion. These findings reveal heterogeneity in CAF responses and link the inflammatory CAF phenotype to reduced RV efficacy, underscoring the importance of CAF subtyping for predicting therapeutic outcomes. This work supports personalised, stroma-targeted strategies to overcome BC progression and resistance.
SN - 1507-1367
SN - 2083-4640
ER -