| First Author | Gu Y | Year | 2019 |
| Journal | Nat Med | Volume | 25 |
| Issue | 2 | Pages | 312-322 |
| PubMed ID | 30643287 | Mgi Jnum | J:306054 |
| Mgi Id | MGI:6711145 | Doi | 10.1038/s41591-018-0309-y |
| Citation | Gu Y, et al. (2019) Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG. Nat Med 25(2):312-322 |
| abstractText | Primary tumors may create the premetastatic niche in secondary organs for subsequent metastasis. Humoral immunity contributes to the progression of certain cancers, but the roles of B cells and their derived antibodies in premetastatic niche formation are poorly defined. Using a mouse model of spontaneous lymph node metastasis of breast cancer, we show that primary tumors induced B cell accumulation in draining lymph nodes. These B cells selectively promoted lymph node metastasis by producing pathogenic IgG that targeted glycosylated membrane protein HSPA4, and activated the HSPA4-binding protein ITGB5 and the downstream Src/NF-kappaB pathway in tumor cells for CXCR4/SDF1alpha-axis-mediated metastasis. High serum anti-HSPA4 IgG was correlated with high tumor HSPA4 expression and poor prognosis of breast cancer subjects. Our findings identify a key role for tumor-educated B cells and their derived antibodies in lymph node premetastatic niche formation, providing potential targets for cancer intervention. |
