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 10 28
ISSN1872-7980
KeywordsAnimals, Apoptosis, Breast Neoplasms, Cell Communication, Cell Movement, Cells, Cultured, Chemokine CCL5, Disease Progression, Electronic Nicotine Delivery Systems, Female, Humans, Lung Neoplasms, Mice, Mice, Inbred BALB C, Tumor Microenvironment, Tumor-Associated Macrophages, Vascular Cell Adhesion Molecule-1
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