Abstract 3848: Smoking promotes angiogenesis and epithelial to mesenchymal transition in breast cancer

Introduction: Nicotine, the addictive component of cigarettes, induces tumor progression via the α7-nicotine acetylcholine receptor (α7-nAChR) subtype in lung cancer. However, the molecular mechanisms by which nicotine impacts tumor progression of breast cancer (BC) remain unclear. In this study, we evaluated the effects of nicotine/smoking on tumor angiogenesis, and epithelial-mesenchymal transition (EMT) signaling mechanisms that are involved in BC progression. Experimental Design: BC cell spheroids from the MCF7, a non-invasive cell line was treated with nicotine (0.3 to 3μM) for 14 days. Sections of tumor tissue from the human BC (smoking vs. never smoking) were assessed for phenotypic expressions of α7-nAChR, and vimentin by immunostaining (IHC). CD31 staining was used to evaluate tumor angiogenesis, as measured by microvessel density (MVD). Western blot (WB) analyses were also performed on lysates of both cell lines and tumors to assess the effect of nicotine on the signaling pathways that promote BC progression. Results: The present study revealed that nicotine treated spheroids have increased expression of Ki67, Mdr1, Oct4 signatures that are indicative of BC progression. IHC analysis indicated that tumor from patients that smoked displayed increased expression of α7-nAChR. Furthermore, the expression of Oct4 (marker for cancer stem-cell), and vimentin (marker for EMT) that correlates with advanced disease and metastasis were found to be higher in smokers. However, tumors from non-smokers had low expression of Oct4 and vimentin. It was also found that tumors from patients who smoked had well established vascularity, while tumors from non-smokers had very little vascularization. Indeed, the mean MVD was lower in tumors from non-smokers compared to tumors from smokers. Conclusions: These findings offer significant novel insights into the mechanism by which nicotine contributes to the increased aggressiveness of BC. This work was supported in part by NIH/NCI Workforce Diversity Grant R21-CA171251. Citation Format: Venkat Katkoori, Shreeya R. Kandukuri, Madhukar V. Burra, James E. Trosko, Deimante M. Tamkus, Cherly Leece, Lakshimipathi R. Kareti, George S. Abela, Harvey L. Bumpers. Smoking promotes angiogenesis and epithelial to mesenchymal transition in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3848.