Abstract 920: ICAM-1(CD54) is involved in the osteogenic differentiation of mesenchymal stem cells and affects the progression of osteosarcoma cells

Abstract

Abstract Purpose: The aim of this study is to validate the relationship between the expression of ICAM-1(CD54), a cell surface glycoprotein, and osteogenic differentiation of mesenchymal stem cells (MSCs) and the role of ICAM-1 in the progression of osteosarcoma (OS) cells. Experimental Design: To compare the gene expression profiles between MSCs and MSCs after osteogenic induction, a microarray analysis was first performed. The differences in expression of specific genes including ICAM-1 were confirmed using western blot and flow cytometry. MSCs were sorted into two groups of cells by CD105+CD44+CD54+ and CD105+C44+CD54- and properties of these cells were compared. Expression of ICAM-1 among tumor cell lines and xenograft OS cells were tested at the protein level. ICAM-1 was stably, constitutively overexpressed in multiple cell types. Differences in osteogenic differentiation potential between normal cell lines and transformed cell lines were studied using alizarin red S staining. Motility, proliferation and invasion as well as the metastatic potential of the transformed and normal cells were evaluated. Results: The initial microarray analysis revealed that ICAM-1 expression was significantly increased in MSCs after osteogenic induction for 15 days (p=0.042). Consistent results were achieved in western blot and flow cytometry analysis. Further microarray analysis between CD105+CD44+CD54+ and CD105+C44+CD54- groups determined that NF-kB signaling pathway was differentially activated. As for OS cells, ICAM-1 is not expressed at high level among OS tumor cell lines and is inconsistently expressed in xenograft OS cells. Enhanced osteogenic differentiation potential was observed in ICAM-1 overexpressing cells. Although there were no major difference in in vitro motility, proliferation or invasion tests, substantially less lung nodules occurred with transformation as compared to the normal control. Conclusions: ICAM-1 is involved in the osteogenic differentiation of mesenchymal stem cells and its down regulation may be involved in the progression of osteosarcoma cells. Citation Format: Yidan Zhang, Sajida Piperdi, Nikolas Zaphiros, Pratistha Koirala, Tingting Ren, Michael Roth, Jonathan Gill, Bang Hoang, David Geller, Rui Yang, Wendong Zhang, Xiuquan Du, Jinghang Zhang, Richard Gorlick. ICAM-1(CD54) is involved in the osteogenic differentiation of mesenchymal stem cells and affects the progression of osteosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 920. doi:10.1158/1538-7445.AM2017-920