The role of CD24 in multiple myeloma tumorigenicity and effects of the microenvironment on its expression
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Nechama Gilad1,2, Hila Zukerman1,3, Marjorie Pick1,* and Moshe E. Gatt1,*
1 Department of Hematology, Sharett Institute, Hadassah Medical Organization, Kiryat Hadassah, Jerusalem, Israel
2 Department of Chemistry and Biology, Hebrew University, Jerusalem, Israel
3 Department of Biomedical Engineering, Technion Institute of Technology, Haifa, Israel
* These authors contributed equally to this work
Keywords: multiple myeloma; CD24; microenvironment; cell cycle and apoptosis changes; tumorigenicity
Received: April 01, 2019 Accepted: August 12, 2019 Published: September 10, 2019
Multiple myeloma (MM) is an incurable neoplasm characterized by infiltration of malignant plasma cells (PCs). Recently, the tumor microenvironment has become of great interest in MM as it known to be involved in progression and metastasis of the disease. CD24, is an adhesion molecule expressed during B cell maturation, is down regulated through the cells differentiation into PCs. Though the role of CD24 in solid cancers is well defined, its role in MM remains unknown. We aimed to understand the involvement of CD24 in MM by up-regulating its expression on MM cell lines by co-culturing the cells with bone marrow stromal cell (BMSCs). We then studied the differences between CD24+ and CD24− MM cells and found that CD24+ MM cells presented a less tumorigenic phenotype by impaired capability to migrate and to create colonies as compared with CD24− MM cells. Furthermore, there were significantly more apoptotic cells in the CD24+ fraction. Additionally, the CD24+ cells also upregulated CXCR4 expression. The decrease tumorigenicity correlated with a “more normal” PC immunophenotype in patients with MM and correlated with CD45 expression and a stronger expression of CXCR4. In summary, we found the expression of CD24 on PCs to correlate with attenuated tumorigenicity.
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