Chidube Ogbonna

Introduction. Breast cancer is the most frequently diagnosed malignancy among women worldwide.¹ It is responsible for more that 4100 deaths per year in the USA.¹ 20-30% of breast cancer patients may develop metastases after diagnosis and primary tumor treatment, and approximately 90% of cancer related deaths are attributed to metastasis.¹ Studies have found that B cells play a role in breast cancer metastasis in mice.²  B cells are commonly known for immunoglobulin production and production of anti-tumor antibodies. However, when B cells are depleted, tumor growth is suppressed in mice. Recent studies have found that B cells can produce pathogenic IgG that can activate CXCR4/SDF1a-axis mediated metastasis through a series of steps.^2. Other studies suggest that inhibition of the CXCR4/SDF1a pathway has the therapeutic capacity of delaying breast cancer metastasis.² AMD3100, a CXCR4 blocker, is one promising therapeutic agent.³ Methods. A mouse model of spontaneous lymph node metastasis of breast cancer was used. B cells were purified using flow cytometer to measure cytokine and immunoglobulin production. IgG was purified from mouse serum. Six-week old female mice were used for tail vein injection or mammary orthoptic implantation. Results. After tumor inoculation, mice showed a greater accumulation of B cells in draining lymph nodes compared to normal mice.² The B cells in the draining lymph nodes showed high levels of pathogenic IgG and they were bound to HSPA4.² ITGB5, HSPA4’s binding protein, phosphorylated Src and activated the NF-kB pathway.² Once activated, Cox2 increased the secretion of SDF1a and Hif1a upregulated CXCR4.² AMD3100 blocked CXCR4 and reduced fibrosis and immunosuppression in mice.³ This improved T cell infiltration which helps prevent metastasis.³ Conclusions. Studies have found that B cells in tumor bearing mice can promote metastasis through the CXCR4/SDF1a pathway. Blocking this pathway using promising therapeutic agents like, AMD3100, can potentially help delay metastasis and lower cancer related deaths.

1. Liang Y, Zhang H, Song X, Yang Q. Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol 2020;60:14-27. doi:10.1016/j.semcancer.2019.08.012
2. Gu Y, Liu Y, Fu L, et al. Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG. Nat Med. 2019;25(2):312-322. doi:10.1038/s41591-018-0309-y
3. Zhang J, Chen J, Wo D, et al. LRP6 Ectodomain Prevents SDF-1/CXCR4-Induced Breast Cancer Metastasis to Lung. Clin Cancer Res 2019;25(15):4832-4845. doi: 10.1158/1078-0432.CCR-18-3557