E-cigarette advocates and pro-tobacco forces generally love to point on that nicotine does not cause cancer. While they are correct that nicotine does not cause cancer, i.e., does not lead to cancer initiation, the fact is that once someone has cancer, nicotine makes it worse. In particular, nicotine promotes growth of blood vessels into tumor (tumor angiogenesis), which is necessary for the cancer to grow, as well as promoting metastasis (spread of the cancer to other sites).
Consistent with these broader effects of nicotine, I recently came on a 2020 paper by Kien Pham and colleagues’ “E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1” that shows than e-cigarette exposure promoted breast cancer and lung metastasis in mice.
They exposed mice to an e-cigarette aerosol produced from an eliquid that was a mixture of 50:50 PG/VG and nicotine (24 mg/mL) and found reduced breast cancer cell death and and increased cell proliferation after e-cig exposure. In isolated cell studies they identified specific molecular pathways that helped explain the effects on breast cancer.
This study is important because it shows that the general results about nicotine being a cancer promoter apply to e-cigarettes. In addition, while we do not yet know the specific cancer risks e-cigarettes pose to people, this study adds to the evidence that it is not zero just because nicotine is not a carcinogen (tumor initiator).
Here is the 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.
The full citation is: Pham K, Huynh D, Le L, Delitto D, Yang L, Huang J, Kang Y, Steinberg MB, Li J, Zhang L, Liu D, Tang MS, Liu C, Wang H. E-cigarette promotes breast carcinoma progression and lung metastasis: Macrophage-tumor cells crosstalk and the role of CCL5 and VCAM-1. Cancer Lett. 2020 Oct 28;491:132-145. doi: 10.1016/j.canlet.2020.08.010. Epub 2020 Aug 21. PMID: 32829009; PMCID: PMC9703643. It is available here.
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