Breast-Cancer-Derived Secretomes from MCF-7 Cells Modulate Bacterial Pathogenic Traits

TL;DR

This study shows how breast cancer cells can change the behavior of bacteria in the tumor environment, potentially affecting disease progression.

Contribution

The study reveals species-specific bacterial reprogramming by breast cancer-derived secretomes, offering new insights into tumor-microbiome interactions.

Findings

MCF-7 conditioned media caused structural changes in Pseudomonas aeruginosa and Enterococcus faecalis.

E. coli showed increased biofilm formation and altered antibiotic susceptibility in response to MCF-7 CM.

MCF-7 CM enriched virulence genes in bacteria, suggesting enhanced pathogenic potential.

Abstract

Breast cancer is the most frequently diagnosed malignancy among women worldwide, with the luminal A subtype being the most prevalent. Several studies have reported a complex interplay between breast cancer cells and the local microbiome; however, the mechanisms by which tumor cell-secreted factors influence bacterial biological properties remain insufficiently explored. In this study, we established an in vitro model that partially recapitulates the luminal A breast cancer microenvironment by exposing three breast-associated bacterial species, Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, to conditioned media (CM) derived from MCF-7 (tumor) or MCF-10A (non-tumor control) cell lines. A combination of complementary approaches, including ultrastructural morphological assessment, biofilm formation assays, antimicrobial susceptibility testing, and virulence gene abundance profiling by genomic qPCR, was employed to reveal distinct tumor-microbiota interactions. Exposure to MCF-7 CM induced dose-dependent structural alterations in P. aeruginosa and E. faecalis, with pronounced membrane blebbing and structural disruption in E. faecalis. Biofilm formation was differentially modulated in a species- and concentration-dependent manner, with a persistent increase observed in E. coli. Antibiotic susceptibility profiles were selectively altered in E. faecalis, which displayed increased sensitivity to vancomycin, penicillin, and imipenem, along with decreased sensitivity to chloramphenicol. P. aeruginosa exhibited increased sensitivity to imipenem along with reduced sensitivity to meropenem and gentamicin, whereas no significant changes were observed in E. coli. qPCR analyses demonstrated that MCF-7 CM was associated with enrichment of multiple virulence-associated genes (e.g., lasB, exoS, pilB, plcH, fsrC, esp, fimH, and papG), reflecting enhanced pathogenic and adhesive potential. Collectively, these findings suggest that luminal A breast cancer-derived factors can reprogram microbial phenotypes in a species-specific manner, providing mechanistic insight into breast tumor-microbiome crosstalk and a platform to explore microbiome-targeted interventions.

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