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

Kien Pham, Do Huynh, Le Le, Daniel Delitto, Lei Yang, Jing Huang, Yibin Kang, Michael B. Steinberg, Jieliang Li, Lanjing Zhang, Dongfang Liu, Moon Shong Tang, Chen Liu, He Wang

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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 α4β1. 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.

Original languageEnglish (US)
Pages (from-to)132-145
Number of pages14
JournalCancer Letters
Volume491
DOIs
StatePublished - Oct 28 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Breast cancer
  • CCL5
  • E-Cigarette
  • Lung metastasis
  • Macrophages
  • V-CAM-1

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