Abstract C075: Effects of lactobacillus plantarum and lactobacillus reuteri on pro-oncogenic phenotypes in inflammatory breast cancer

Abstract Introduction: Inflammatory breast cancer (IBC) is the most lethal form of breast cancer characterized by rapid metastasis and poor prognosis. African American, Hispanic/Latina, and North African women are particularly susceptible to developing this type of breast cancer. Current therapeutic options are limited, with a 5-year survival rate of approximately 30-60%, highlighting the need for novel treatment strategies. Growing evidence suggests that microbial imbalance (dysbiosis) in the microbiome is linked to cancer progression. Previous studies indicate that probiotic bacteria commonly found in breast tissue microbiota, such as Lactobacillus plantarum (L. plantarum) exhibit anti-cancer properties in pancreatic cancer cells, while Lactobacillus reuteri (L. reuteri) had similar effects in colorectal cancer cells. Studies suggest that bacteria may influence cancer progression by modulating macrophages in the tumor microenvironment (TME). Macrophages can polarize into M1 (anti-tumorigenic) or M2 (pro-tumorigenic) phenotypes in response to local stimuli. Objectives: The main goal of this study was to assess the effects of L. plantarum and L. reuteri on oncogenic phenotypes (viability, proliferation, invasion and migration) in IBC. Also, investigate whether these bacteria influence cancer progression by polarizing macrophages (M1 or M2) in the TME. Methods: SUM149PT and SUM190 cells were treated with different concentrations of L. plantarum and L. reuteri supernatants for 24-hours, and cell viability was assessed using the resazurin assay. The (IC50) for bacteria was determined by creating a dose-response curve. Cell migration was assessed by seeding SUM149PT cells in a 6-well plate until confluence, a wound was created, and bacteria were added at different concentrations for 19-hours. For macrophage polarization, we will grow THP-1 monocytes and differentiate them into macrophages M0 using 150 nM phorbol 12-myristate 13-acetate (PMA) for 24-hours. Then, add them in a co-culture with bacteria-treated SUM149PT and leave them to interact for 24-, 48-, and 72-hours and assess macrophage polarization using Western Blot analysis and measure markers for each macrophage phenotype: CD206 and Arg-1 (M2) and CD86 and iNOS (M1). Results: A 24-hour treatment with bacterial supernatant decreased cell viability, yielding IC50 values of 21 (v/v%) for L. plantarum supernatant and 9 (v/v%) for L. reuteri supernatant in SUM149PT cells, and 7 (v/v%) for L. plantarum supernatant and 5 (v/v%) for L. reuteri supernatant in SUM190 cells. Additionally, L. plantarum (p = 0.01) and L. reuteri (p < 0.05) reduced cell migration in SUM149PT cells at 19-hours. Conclusion: This study demonstrates that L. plantarum and L. reuteri can reduce cell viability and cell migration in IBC cells. These findings suggest that modulating the microbiome represents a potential approach for the treatment and prevention of IBC. For future directions, we will further explore the molecular mechanisms through which these bacteria influence cancer progression. Citation Format: Ayub Napel Shahada, Yabdiel A. Ramos-Valerio, Dr. Esther Peterson-Peguero. Effects of lactobacillus plantarum and lactobacillus reuteri on pro-oncogenic phenotypes in inflammatory breast cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C075.