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Tumor-educated B Cells Selectively Promote Breast Cancer Lymph Node Metastasis by HSPA4-targeting IgG

Tumor-educated B Cells Selectively Promote Breast Cancer Lymph Node Metastasis by HSPA4-targeting IgG

Yan Gu, Yanfang Liu, Li Fu, Lili Zhai, Jie Zhu, Yanmei Han, Yingming Jiang, Yi Zhang, Peng Zhang, Zhengping Jiang, Xiang Zhang, Xuetao Cao

Nat Med. 2019 Feb;25(2):312-322.

PMID: 30643287

Abstract:

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-κB pathway in tumor cells for CXCR4/SDF1α-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Price
IAR4241047	Heat Shock Protein 25 from mouse	Price
IAR4248638	Stromal Cell-Derived Factor 1α/pre-B Cell Growth Stimulating Factor from mouse	Price
IAR4248681	SDF-1alpha (CXCL12) from mouse	Price

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