B cells promote the growth and stem-like qualities of breast cancer cells in the bone marrow

Bone metastasis is a critical factor in the morbidity and mortality of breast cancer patients, yet the specific contributions of the bone marrow microenvironment to this process remain incompletely understood. We investigated the influence of bone marrow cell populations on intraosseous tumor growth following the injection of E0771 breast cancer cells into the bone. Kinetic analysis revealed a progressive reduction in CD19 + CD20 + B220 + immature B cells as the tumor burden increased. Depletion of CD20 + immature B cells, but not CD19 + CD20 - B220 + pro/pre-B cells, significantly increased the intraosseous tumor burden along with upregulation of the proliferation marker Ki-67. To simulate the bone cavity environment, we employed anchorage-independent in vitro co-cultures of tumor cells with B-cell populations. Using this co-culture system, pro/pre-B cells, but not immature B cells, enhanced tumor cell proliferation with upregulation of Ki-67. Mechanistically, pro/pre-B cells enhanced tumor cell proliferation through the production of soluble factors and promoted stem cell-like properties, as indicated by increased expression of the stem cell marker CD44. By analyzing clinical datasets from breast cancer patients, we found that high CD20 expression correlated with longer overall survival, thereby supporting a positive correlation between increased immature B cells and better control of disease progression. Collectively, these results indicate contradictory roles for CD20 - pro/pre-B cells and CD20 + immature B cells in controlling the tumor microenvironment in bone.