Silencing of TLR4 Increases Tumor Progression and Lung Metastasis in a Murine Model of Breast Cancer

• Published in: Annals of surgical oncology 2013-12, Vol.20 (Suppl 3), p.389-396
• Main Authors: Ahmed, Abubakr, Wang, Jiang Huai, Redmond, H. Paul
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Blotting, Western; Cell Adhesion; Cell Proliferation; Disease Models, Animal; Female; Gene Silencing - physiology; Killer Cells, Natural - metabolism; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - secondary; Mammary Neoplasms, Animal - genetics; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Nude; Oncology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Surgery; Surgical Oncology; T-Lymphocytes, Cytotoxic - metabolism; Toll-Like Receptor 4 - genetics; Translational Research and Biomarkers; Tumor Cells, Cultured
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-012-2595-9

Background Toll-like receptor 4 (TLR4) is a member of a family of pattern recognition receptors that are involved in the host defense against microbial infection. Little research has investigated the link between TLR4 and cancer. We thus addressed the effect of TLR4 in both the host immune system and cancer cells with regard to its effect on breast cancer progression and metastasis. Methods Adult female Balb/c mice aged 6–8 weeks were divided into three groups. In group 1, 15 each wild-type and TLR4 −/− mice were inoculated with 4T1 cells; in group 2, wild-type mice were inoculated with 4T1 cells ( n  = 15), 4T1 cells transduced with TLR4 lentivirus ( n  = 15) or with control lentivirus ( n  = 15); and in group 3, 15 TLR4 −/− mice were inoculated with 4T1 cells transduced with TLR4 lentivirus. Flank tumor volume was measured with calipers during weeks 2–5. Animals were then humanely killed and the number of macroscopic lung nodules counted. Results There was a significant increase in tumor volume in weeks 2, 3 and 4 after inoculation of TLR4 −/− mice with 4T1 cells compared with wild-type mice ( p