In vivo homing and differentiation characteristics of mature (CD45(-)) andimmature (CD45(+)) 5T multiple myeloma cells

Objective. Multiple myeloma, a plasma tell malignancy, is predominantly loc alized in the bone marrow. These tumoral cells display a heterogeneous expr ession of CD45. It is, however, unclear which subpopulation is responsible for the homing and outgrowth of the myeloma cells. In this work, we investi gated the in vivo homing, proliferation, and differentiation of both CD45() and CD45(-) cells in two murine myeloma models. Materials and Methods. 5T2MM and 5T33MM in vivo lines of murine multiple my eloma were used. CD45 and IGF-I receptor expression was analyzed by FAGS. P roliferative capacity was assessed by in vivo bromodeoxyuridine incorporati on. 5TMM cells wee separated into CD45(+) and CD45(-) fractions by MACS. In itial homing was investigated in vivo by tracing of radioactively labeled c ells, Myeloma cells were detected by FAGS and histology, Osteolytic lesions were analyzed by radiography, Results, Both CD45(+) and CD45(-) 5TMM cells were able to home to the bone marrow, although the migration of the latter subset was lower, which was re lated to a low IGF-I receptor expression, Recipients of both fractions deve loped myeloma as evidenced by the presence of serum paraprotein, osteolytic lesions, and bone marrow infiltration by myeloma cells. The tumor load in the recipients of CD45(-) tells was higher than the CD45(+) cells, which co uld be explained by a lower proliferation rate of the latter population, Wh ile the separated cells before injection had a homogenous expression of CD4 5, cells isolated from the hone marrow of these terminally diseased mice ha d a heterogeneous expression pattern, indicating an in vivo differentiation pattern of CD45(-) to CD45(+) cells and vice versa, Conclusion. We conclude that both CD45(+) and CD45(-) 5TMM subpopulations c ontain clonogenic myeloma tells with hone marrow homing and proliferative c apacity. (C) 2001 International Society for Experimental Hematology. Publis hed by Elsevier Science Inc.