The Role of CD24 in Multiple Myeloma Tumorigenicity and the Effect of the Microenvironment on CD24 Expression

Background: Multiple myeloma (MM) is a mature B cell neoplasm characterized by clonal proliferation of plasma cells (PC). It is believed that its microenvironment of cell growth and survival. An important B cell differentiation antigen is CD24, a cell adhesion molecule, which is expressed at high levels from early stage of B cell precursors and undergoes downregulation as the cell matures to a PC. In this work we tried to unfold the role of CD24 in MM and explain the effects of the microenvironment on CD24 expression.

Methods: We induce the expression of CD24 on normal B cells and Multiple myeloma (MM) cell lines with the aid of bone marrow stromal cells generated from samples of MM patients bone marrow. After induction the differences between CD24+ and CD24- on B and MM cells determine changes tumorigenicity of two fractions of cells were studied.

Results: Expression of CD24 was low on immortalized B and MM cell lines, but significantly elevated after co-culture with bone marrow stromal cells generated from MM patients. Expression levels varied in concordance with the patient disease status. We further studied the differences between sorted CD24+ and CD24- B and MM cells by analyzing their cell cycle, their ability to migrate through a membrane and to form colonies in methylcellulose. We found that the CD24+ cells form less colonies, migrate less and have an increased apoptosis population compared with CD24- cells. We further validated our results by analyzing CD24 expression in primary PCs from BM samples of patients in different MM stages of disease. We found that CD24 was expressed significantly higher on PCs from patients with inactive MM, as compared with patients with active MM. Our findings show that CD45+ PCs express a significantly higher percent of CD24 than CD45- cells. These results also reinforce our in vitro result regarding the correlation between CD24 expression and decreased tumorigenicity. We also show correlation between CD24 expression and CXCR4 intensity, thus hypothesizing a possible mechanism for our results.

Conclusions: In this study, we found that up-regulation of CD24 expression on MM cell lines caused apoptosis of the cells and reduced their tumorigenicity. This effect was robust and the process is specific. In addition, we show that the process regulated by BMSCs cells, and in correlation to the patient's MM state. We hypothesize that it is mediated through direct contact and partially explained by an interaction with CXCR4. Our results clearly indicate a correlation between CD24 and reduced MM aggressiveness. Targeting an increase in the CD24 expression in these cells could be a potential therapy and marker in the future.