J Cancer 2017; 8(12):2212-2222. doi:10.7150/jca.18808

Research Paper

Reelin promotes adhesion of multiple myeloma cells to bone marrow stromal cells via integrin β1 signaling

Liang Lin1#, Xinwei Zhang1#, Li Cao1, Quanming An1, Jie Hao1, Yan Zhang1, Rong Jin1, Yingjun Chang2, Xiaojun Huang2, Jin Lu2✉, Qing Ge1✉

1. Key Laboratory of Medical Immunology, Ministry of Health. Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xue Yuan Road, Beijing, P. R. China, 100191
2. Peking University Institute of Hematology, People's Hospital, Beijing, China, 100044
# L.L. and X.Z. contributed equally to this work

Abstract

The close interaction between tumor cells and bone marrow stromal cells plays a crucial role in the tumorigenesis of multiple myeloma (MM). Reelin, an extracellular matrix protein, is found expressed in myeloma cells and is negatively associated with prognosis. We examined the role of Reelin in myeloma cell adhesion to bone marrow stromal cells and the signaling pathways involved. The results revealed that Reelin promoted the adhesion of myeloma cells to HS-5, a bone marrow stromal cell line, via the activation of β1 integrin. The resulting phosphorylation of focal adhesion kinase (FAK) led to the activation of Syk/STAT3 and Akt. Reelin's high affinity receptor ApoER2 indirectly modulated the adhesion of myeloma cells by promoting Reelin expression via Sp1. These findings indicate an important role for Reelin/integrin-β1-induced myeloma cell adhesion to bone marrow stromal cells and highlight the therapeutic potential of targeting Reelin/integrin/FAK axis.

Keywords: Reelin, multiple myeloma, bone marrow stromal cells, adhesion, integrin

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Lin L, Zhang X, Cao L, An Q, Hao J, Zhang Y, Jin R, Chang Y, Huang X, Lu J, Ge Q. Reelin promotes adhesion of multiple myeloma cells to bone marrow stromal cells via integrin β1 signaling. J Cancer 2017; 8(12):2212-2222. doi:10.7150/jca.18808. Available from http://www.jcancer.org/v08p2212.htm