Page 118 - D. Cancer biology
P. 118
[D. Cancer biology-74]
Activation of the Sympathetic Nerve System Weakens Anti-
Tumoral Immunity via Beta 2 Adrenergic Receptors in
Osteoblast and Myeloid-Derived Suppressor Cells,
Contributing to Bone Metastasis Progression
Eun Jung Lee¹, Kyoung Jin Lee¹, Serk In Park¹˙*
¹Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 02841, Korea
The sympathetic nerve system (SNS) regulates bone homeostasis via beta 2 adrenergic receptor (Adrb2) on
osteoblasts, and chronic stress-induced SNS activation was shown to promote bone metastasis tumor growth via
osteoblastic cytokine expression in immunocompromised mouse models. We further investigated the effects of SNS
activation on immune cells in the bone microenvironment using immune-competent mouse models of breast cancer
bone metastasis. Chronic immobilization stress (CIS) increased 4T1 syngeneic breast tumor growth in bone that was
reversed by administration of ICI-118551, a pharmacologic inhibitor of Adrb2. Moreover, CIS-treated tumors had
increased CD11b+Gr1+ myeloid-derived suppressor cells (MDSC). Two-week CIS pre-treatment before intra-tibial
tumor implantation increased EdU+ proliferating MDSC, supporting that CIS primes the pre-metastatic niche in
bone by tipping anti-tumoral immunity balance in favor of tumor growth. In addition, isoproterenol increased C-C
chemokine ligand-2, one of the known inducers of MDSC expansion, in MC3T3E1 osteoblasts. Our data collectively
demonstrate that activation of the SNS contributes to breast cancer bone metastasis partly by expanding MDSC.
The SNS activation-dependent MDSC expansion is mediated by osteoblastic Adrb2.
