Figure 1.
Tissue -resident MPs promote dissemination of myeloma and disease progression. (A) Sample plots and analysis of MP (CD11blowF4/80+) frequencies in the BM in CD169-DTR mice before and after treatment with DT; data were pooled from total myeloid cells (CD11b+), monocytes (CD11b+Ly6Chi), neutrophils (CD11b+Ly6Ghi), and MPs normalized to untreated controls. (B) Tumor burden analyzed in paired injected (inj; blue) and contralateral (CL; green) tibias of DT-treated CD169-DTR mice and control mice at 5 weeks after intratibial tumor inoculation and calculated dissemination index (ratio of myeloma burden in contralateral BM to that in injected BM). (C) Experiment setup as in panel B, with DT treatments starting at 2 weeks post tumor challenge (ptc). (D) Survival analysis (using Mantel-Cox test) of DT-treated or untreated CD169-DTR mice after intratibial tumor inoculation as in panel B. (E) Analysis of M-spike levels at 5 weeks and 20 weeks post tumor challenge in survival study shown in panel D. (F) Tumor burden was analyzed in DT-treated CD169-DTR (DTR+DT) mice and control (WT+DT) mice at 5 weeks after intravenous inoculation. (G) Analysis of tumor burden and dissemination index in chimeric hosts generated from lethal irradiation of recipient mice and reconstitution with donor BM cells, as labeled. Data from multiple experiments were pooled. All experiments were independently repeated 2 to 5 times, and each dot presents an individual mouse. Data comparisons were analyzed by using a Mann-Whitney t test. Error bars represent standard deviation. *P < .05; **P < .01; ***P < .001; ****P < .0001. n.s., not significant.