regulation of cox2 expression in mouse mammary tumor cells controls bone metastasis and pge2-induction of regulatory t cell migration监管cox2的表达在小鼠乳腺肿瘤细胞控制骨转移和pge2-induction调节性t细胞的迁移.pdfVIP

Regulation of COX2 Expression in Mouse Mammary Tumor Cells Controls Bone Metastasis and PGE2- Induction of Regulatory T Cell Migration 1,2 1,2 1,2 2 2 John Karavitis , Laura M. Hix , Yihui H. Shi , Rachael F. Schultz , Khashayarsha Khazaie , Ming Zhang1,2* 1 Departments of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America, 2 Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America Abstract Background: The targeting of the immune system through immunotherapies to prevent tumor tolerance and immune suppression are at the front lines of breast cancer treatment and research. Human and laboratory studies have attributed breast cancer progression and metastasis to secondary organs such as the bone, to a number of factors, including elevated levels of prostaglandin E2 (PGE2) and the enzyme responsible for its production, cyclooxygenase 2 (COX2). Due to the strong connection of COX2 with immune function, we focused on understanding how variance in COX2 expression manipulates the immune profile in a syngeneic, and immune-competent, mouse model of breast cancer. Though there have been correlative findings linking elevated levels of COX2 and Tregs in other cancer models, we sought to elucidate the mechanisms by which these immuno-suppressive cells are recruited to breast tumor and the means by which they promote tumor tolerance. Methodology/Principal Findings: To elucidate the mechanisms by whic