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肿瘤教育 B 细胞通过诱导 IL-1β/HIF-2α/Notch1 信号促进肾癌转移。

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

机构信息

Department of Urology, Shanghai Tenth People's Hospital, Nanjing Medical University, 211166, Nanjing, China.

Department of Urology, the Affiliated Changzhou Maternity and Child Health Care Hospital of Nanjing Medical University, 16 DingxiangRoad, Zhonglou District, 213000, Changzhou, Jiangsu, China.

出版信息

Cell Death Dis. 2020 Mar 2;11(3):163. doi: 10.1038/s41419-020-2355-x.

DOI:10.1038/s41419-020-2355-x
PMID:32123166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7052134/
Abstract

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.

摘要

虽然肿瘤微环境（TME）中的 B 细胞可能在癌症进展中发挥重要作用，但它们对肾细胞癌（RCC）转移的影响尚不清楚，这引起了我们的关注，需要进一步探索。我们发现，从人类临床 RCC 样本中，RCC 组织比周围正常肾组织招募了更多的 B 细胞。伤口愈合试验、Transwell 试验和 3D 侵袭试验表明，募集的 B 细胞，也称为肿瘤教育的 B 细胞（TEB），可以显著增加 RCC 细胞的迁移和侵袭。此外，来自异种移植 RCC 小鼠模型的体内数据也证实，TEB 可以增强 RCC 细胞的侵袭和转移能力。机制剖析表明，TEB 在 RCC 细胞中激活了 IL-1β/HIF-2α 信号，可诱导下游 Notch1 信号通路。上述结果表明，TEB 在肾肿瘤相关肿瘤微环境中的关键作用是促进转移，并且可能有助于我们通过靶向这些新鉴定的 IL-1β/HIF-2α/Notch1 信号通路来开发针对 RCC 进展的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/757e68fbceda/41419_2020_2355_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/34ed985b2bc1/41419_2020_2355_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/ccfb3738432f/41419_2020_2355_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/496c8fd9ab9d/41419_2020_2355_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/db224fed3086/41419_2020_2355_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/30f5f32899ce/41419_2020_2355_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/9e0932dafc72/41419_2020_2355_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/757e68fbceda/41419_2020_2355_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/34ed985b2bc1/41419_2020_2355_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/ccfb3738432f/41419_2020_2355_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/496c8fd9ab9d/41419_2020_2355_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/db224fed3086/41419_2020_2355_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/30f5f32899ce/41419_2020_2355_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/9e0932dafc72/41419_2020_2355_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d71/7052134/757e68fbceda/41419_2020_2355_Fig7_HTML.jpg

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