Tumor microenvironment B cells increase bladder cancer metastasis<i>via</i>modulation of the IL-8/androgen receptor (AR)/MMPs signals

Ou, Zhenyu; Wang, Yongjie; Liu, Longfei; Li, Lei; Yeh, Shuyuan; Qi, Lin; Chang, Chawnshang

doi:10.18632/oncotarget.4569

Cited by 87 publications

(72 citation statements)

References 34 publications

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“…Importantly, using the 3D invasion assay (24,25) to replace the Transwell invasion assay, we obtained similar results showing that knocking down ERb in 786-O cells (786-O-shERb) decreased cancer cell invasion (Fig. 1C, left two panels), and overexpressing ERb in A498 cells (A498-oeERb) increased cell invasion ability (Fig.…”

Section: Erb Promoted Ccrcc Cell Invasionsupporting

confidence: 61%

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

et al. 2018

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Early studies have indicated that estrogen receptor beta (ERβ) can influence the progression of clear cell renal cell carcinoma (ccRCC). Here, we report the mechanistic details of ERβ-mediated progression of ccRCC. ERβ increased ccRCC cell invasion via suppression of circular RNA ATP2B1 (circATP2B1) expression by binding directly to the 5' promoter region of its host gene ATPase plasma membrane Ca2 transporting 1 (ATP2B1). ERβ-suppressed circATP2B1 then led to reduced miR-204-3p, which increased fibronectin 1 (FN1) expression and enhanced ccRCC cell invasion. Targeting ERβ with shRNA suppressed ccRCC metastasis in a murine model of RCC; adding circATP2B1 shRNA partly reversed this effect. Consistent with these experimental results, ccRCC patient survival data from The Cancer Genome Atlas indicated that a patient with higher ERβ and FN1 expression had worse overall survival and a patient with higher miR-204-3p expression had significantly better overall survival. Together, these results suggest that ERβ promotes ccRCC cell invasion by altering the ERβ/circATP2B1/miR-204-3p/FN1 axis and that therapeutic targeting of this newly identified pathway may better prevent ccRCC progression. These results identify an ERβ/circATP2B1/miR-204-3p/FN1 signaling axis in RCC, suggesting ERβ and circular RNA ATP2B1 as prognostic biomarkers for this disease. .

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Section: Erb Promoted Ccrcc Cell Invasionsupporting

confidence: 61%

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

et al. 2018

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“…It was widely recognized that B cells could differentiate into plasma cells and produce antibodies after antigen stimulation [5][6][7] . 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 .…”

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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“…These tumor-infiltrating B cells then secrete lymphotoxin, which activates non-canonical and canonical NF-κB signaling and STAT3 in the remaining cancer cells, resulting in androgen-refractory growth and tumor progression [44–46]. Additionally, B cells can also enhance metastasis of bladder cancer cells by upregulating IL-8, which can modulate androgen receptor and matrix metalloproteinase signaling [47]. Lymphotoxin, however, may also contribute to tumor regression in certain tumor settings, and this is discussed in a subsequent section.…”

Section: B Cell Suppression Of the Antitumor Responsementioning

confidence: 99%

B Lymphocytes and Cancer: A Love–Hate Relationship

2016

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Tumor microenvironment B cells increase bladder cancer metastasisviamodulation of the IL-8/androgen receptor (AR)/MMPs signals

Abstract: ABSTRACT

Cited by 87 publications

References 34 publications

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

ERβ-Mediated Alteration of circATP2B1 and miR-204-3p Signaling Promotes Invasion of Clear Cell Renal Cell Carcinoma

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

B Lymphocytes and Cancer: A Love–Hate Relationship

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