E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1.

TitleE-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1.
Publication TypeJournal Article
Year of Publication2020
AuthorsPham, K, Huynh, D, Le, L, Delitto, D, Yang, L, Huang, J, Kang, Y, Steinberg, MB, Li, J, Zhang, L, Liu, D, Tang, M-S, Liu, C, Wang, H
JournalCancer Lett
Volume491
Pagination132-145
Date Published2020 Oct 28
ISSN1872-7980
Abstract

<p>Young women represent a target of E-cigarette (E-cig) companies, raising concern for potential connections with breast cancer (BC) that have not yet been elucidated. We hypothesized that E-cig promotes BC development and lung metastasis possibly through BC-monocyte/tumor-associated macrophage (TAM) crosstalk via CCL5 and V-CAM-1 axes. We demonstrated that E-cig promoted the infiltration of circulating monocytes in mammary fat pad (MFP) model. Furthermore, E-cig exposure significantly enhanced BC cell growth in MFP tumor and metastatic lung colonization; immunohistochemical stains illustrated the increase of TAMs infiltration, reduced BC cell apoptosis and increased proliferation index after E-cig exposure. In vitro studies show E-cig vapor condensate (EVC) treatment upregulated protein expressions of CCL5, V-CAM-1, and other pro-tumorigenic factors in BC cells. Mechanistically, co-culture system demonstrated both EVC and macrophages independently stimulated BC cell growth and the migration via CCL5/CCR1/CCR5 axis. During metastasis, E-Cig exposure stimulated BC cell survival via direct interaction with infiltrated macrophages, regulated by VCAM-1 and integrin αβ1. Our findings, for the first time, showed that E-cig promotes BC growth and metastasis. This study highlights the critical role of TAMs via CCL5 and VCAM-1 pathways in E-cig promoted BC tumor development.</p>

DOI10.1016/j.canlet.2020.08.010
Alternate JournalCancer Lett
PubMed ID32829009
Grant ListR21 HL125018 / HL / NHLBI NIH HHS / United States