Control of Smoke‐Induced Proliferation and Migration of Human Breast Cancer Cells by PK11195, a Translocator Protein (TSPO) Antagonist

Abstract

Cigarette smoking is linked to breast cancer, particularly in young women. However, the exact mechanism is unknown. We have recently established that TSPO is an important biomarker for breast cancer; its expression is increased with an increase in aggressiveness of cancer. The present study investigates whether exposure of mainstream (MS) as well as Sidestream (SS) cigarette smoke induces TSPO‐mediated cell proliferation and migration in a variety of human breast cancer epithelial cell lines and if so whether PK11195, a TSPO antagonist can counteract these effects. Human breast cancer cell lines (MCF10, MCF 12A and MCF 12F) were grown in DMEM/F‐12 and exposed to either MS or SS smoke generated from 1R3F cigarettes in a THRI MS‐SS smoke exposure machine using the modified version of CULTEX cell culture smoke exposure system. A sham control (SH) group was also used where cells were exposed to the same environmental condition without smoke exposure. Induction of cell proliferation and migration was observed at low doses of smoke whereas cellular apoptosis was observed at high doses in all cell lines regardless of MS and SS exposure. A combination of immunohistochemical, Western blot and receptor binding studies revealed an over‐expression of TSPO in all cell lines by both MS and SS smoke. Furthermore, both MS and SS smoke caused a higher level of TSPO in nuclei associated with an increase in nuclear cholesterol transport. The proliferation and migration was controlled when treated with PK11195, suggesting a therapeutic potential of PK11195 in controlling smoke induced breast cancer development. ( Supported by FAMRI Clinical Innovator Award # 062415).