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Macrophage reprogramming by the ultraviolet filter benzophenone-1 promotes malignant phenotypes in breast cancer
Binglu He1,2, Longying Ding3, Xiaolu Yang1,2
1Department of Breast Disease Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
Background:
Benzophenone-1 (BP-1) is a benzophenone ultraviolet absorber used in cosmetic and personal care products. Although BP-1 exhibits estrogenic activity, its broader effects in breast cancer remain unclear. This study investigated the molecular and cellular responses associated with BP-1 exposure.
Methods:
Integrated computational analyses were used to identify core targets and determine their cellular distribution. Molecular modeling evaluated BP-1-target binding. Macrophage polarization and secretion were assessed by immunofluorescence, RT-qPCR, enzyme-linked immunosorbent assay, and western blotting. The effects of macrophage-conditioned medium on breast cancer cells were examined using proliferation, migration, invasion, and epithelial-mesenchymal transition assays.
Results:
PLAUR was identified as the core BP-1-related candidate and was prominently expressed in macrophages. BP-1 increased expression of uPAR, the protein encoded by PLAUR, and shifted macrophages toward an M2-like phenotype. Conditioned medium from these macrophages enhanced malignant phenotypes in breast cancer cells.
Conclusion:
This study identifies a macrophage-associated response to BP-1 exposure that may contribute to malignant phenotypes in estrogen receptor-positive breast cancer, with PLAUR/uPAR as a candidate mediator. These findings provide a basis for further mechanistic and in vivo studies.
