Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG

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

doi:10.1038/s41591-018-0309-y

Cited by 165 publications

(133 citation statements)

References 61 publications

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“…Nevertheless, it was reported that tumoreducated B (TEB) cells contributed to tumor heterogeneity and therapy resistance in melanoma 8 , and participated in bladder tumor progression 9 . Another study found that tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG 10 . These findings supported the hypothesis that educated B cells by tumor and cytokines released from tumor established a stable microenvironment, which made it easier for tumor cells metastasis and colonization.…”

Section: Introduction and Objectivesmentioning

confidence: 99%

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Huang

et al. 2020

Cell Death Dis

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While B cells in the tumor microenvironment (TME) might play important roles in cancer progression, their impacts on the renal cell carcinoma (RCC) metastasis remained unclear, which drew our attention to further explore. We found that RCC tissues could recruit more B cells than the surrounding normal renal tissues from human clinical RCC samples. Wound healing assay, transwell assay and 3D invasion assays demonstrated that recruited B cells, also known as tumor-educated B cells (TEB), could significantly increase the RCC cell migration and invasion. In addition, in vivo data from xenograft RCC mouse model also confirmed that TEB could enhance RCC cell invasive and metastatic capability. Mechanism dissection revealed that TEB activated IL-1β/HIF-2α signals in RCC cells that could induce the downstream Notch1 signaling pathway. The above results demonstrated the key roles of TEB within renal cancer associated tumor microenvironment were metastasis-promotor and might help us to develop the potential therapies via targeting these newly identified IL-1β/HIF-2α/Notch1 signals in RCC progression.

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Section: Introduction and Objectivesmentioning

confidence: 99%

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Huang

et al. 2020

Cell Death Dis

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“…Focal adhesions manipulate the extracellular space by transmitting cytoskeletal forces via integrins (inside‐out signaling) while simultaneously translating external physicochemical cues into signaling that drives the transcription of secreted proteins (outside‐in signaling; Fig. 2) such as those that inhibit tumor cytotoxic T cells 5,6 . Integrins therefore function bidirectionally, meaning information can be transmitted from the outside environment to inside the cell and vice versa 7 .…”

Section: Structure Of Integrinsmentioning

confidence: 99%

The role of integrins in melanoma: a review

et al. 2020

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Integrins are the major family of cell adhesion receptors in humans and essential for a wide range of normal physiology, including formation and maintenance of tissue structure integrity, cell migration, proliferation, and differentiation. Integrins also play a prominent role in tumor growth and metastasis. Translational research has tried to define the contribution of integrins to the phenotypic aggressiveness of melanoma because such knowledge is clinically useful. For example, differential expression of integrins in primary cutaneous melanoma can be used to distinguish indolent from aggressive, prometastatic melanoma.Recent studies have shown that gene expression-based testing of patient-derived melanoma tissue is feasible, and molecular tests may fully replace interventional surgical methods such as sentinel lymph node biopsies in the future. Because of their central role in mediating invasion and metastasis, integrins are likely to be useful biomarkers. Integrins are also attractive candidate targets for interventional therapy. This article focuses on the role of integrins in melanoma and highlights recent advances in the field of translational research.

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“…Further, a key role of tumor-educated B cells on breast cancer lymph node metastasis has been recently described. Here, B cell-derived pathogenic antibodies target the tumor antigen HSPA4 and promote the formation of the premetastatic niche in tumor-draining lymph nodes [57]. Further, we are aware that MCF7 and MDAMB123 cells are biologically different cell types.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Tumor-Lymphatic Interactions in Invasive Breast and Prostate Carcinoma

Oliveira‐Ferrer

Milde‐Langosch

Eylmann

et al. 2020

IJMS

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During the last few years, diverse studies have shown that tumors can actively interact with the lymphatic system and promote metastases development. In order to examine the molecular mechanisms involved in this interaction, we co-cultured tumor and lymphatic endothelial cells (LEC) and subsequently analyzed the molecular alterations of LECs. Therefore, LECs were co-cultivated with either a highly or weakly metastatic breast cancer cell line using contact (mixture) and non-contact (transwell) co-cultures. mRNA profiles from LECs were subsequently analyzed for genes specifically induced by highly metastatic tumor cells (“metastatic specific”). Among the up-regulated “metastatic specific” genes, we found candidates involved in cell cycle, cell adhesion and motility (BST2, E-selectin, and HMMR), cytokines (CCL7, CXCL6, CXCL1, and CSF2) and factors of the complement system (C1R, C3, and CFB). Among the down-regulated genes, we detected the hyaluronan receptor STAB2, angiogenic factor apelin receptor (APLNR), and the glycosylation enzyme MAN1A1. In an additional prostate cancer co-culture model, we could confirm a “metastatic specific” upregulation of E-selectin and CCL7 in LECs after interaction with the prostate cancer cell lines LNCAP (highly metastatic) and DU145 (weakly metastatic). These data allowed us to identify a set of genes regulated in LECs during in vitro communication with cancer cells, which might subsequently facilitate lymphatic metastasis.

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Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG

Cited by 165 publications

References 61 publications

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

Tumor-educated B cells promote renal cancer metastasis via inducing the IL-1β/HIF-2α/Notch1 signals

The role of integrins in melanoma: a review

Mechanisms of Tumor-Lymphatic Interactions in Invasive Breast and Prostate Carcinoma

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