Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model

Zhang Kun; Gao Xin; Wang Tao; Zhao Chenglong; Wang Dongsheng; Tang Liang; Liu Tielong; Xiao Jianru

doi:10.1016/j.jbo.2019.100238

Tumor derived EDIL3 modulates the expansion and osteoclastogenesis of myeloid derived suppressor cells in murine breast cancer model

J Bone Oncol. 2019 Apr 29:16:100238. doi: 10.1016/j.jbo.2019.100238. eCollection 2019 Jun.

Authors

Zhang Kun^{1

2}, Gao Xin^{1

2}, Wang Tao^{1

2}, Zhao Chenglong^{1

2}, Wang Dongsheng^{1

2}, Tang Liang^{1

2}, Liu Tielong^{1

2}, Xiao Jianru^{1

2}

Affiliations

¹ Spine Tumor Center, Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, China.
² East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology, Shanghai, China.

Abstract

Epidermal growth factor-like repeats and discoidin I like domain 3 (EDIL3) is an integrin ligand which is implicated in bone metabolism and bone marrow myelopoiesis. Recently, myeloid derived suppressor cells (MDSCs) as osteoclast progenitor have been demonstrated in several kinds of cancers including breast cancer. In this paper we explored the association between tumor derived EDIL3 and MDSCs in a murine breast cancer model. Knockdown of EDIL3 in MDA-MB-231 breast cancer cells inhibited the expansion of tumor induced MDSCs in bone marrow. However, generation of bone marrow derived MDSCs in vitro was not affected by recombinant EDIL3. Osteoclastogenesis of MDSCs was dose-dependently inhibited by recombinant EDIL3 in vitro via binding to Mac-1 but not LFA-1. Moreover, in accordance with previous studies, our data showed that tumor derived EDIL3 was involved in tumor associated bone loss. The convoluted effects of EDIL3 on MDSCs compose a potential mechanism hired by tumor cells for perpetration approximately.

Keywords: Breast cancer; EDIL3; MDSCs; Osteoclastogenesis.