title: Tumor microenvironment B cells increase bladder cancer metastasis via modulation of the IL-8/androgen receptor (AR)/MMPs signals.
abstract: While B cells in the tumor microenvironment may play important roles in cancer progression, their impacts on the bladder cancer (BCa) metastasis remain unclear. Here we found from human clinical BCa samples that BCa tissues could recruit more B cells than the surrounding normal bladder tissues and the in vitro co-culture assay also demonstrated that B cells could be recruited more easily towards BCa cells compared to normal bladder cells. Chamber invasion and 3D invasion assays showed the recruited B cells could then significantly increase the BCa cell invasion. Mechanism dissection found that recruited B cells could increase IL-8/androgen receptor (AR) signals in BCa cells that could then promote the expression of metastasis genes including MMP1 and MMP13. Blocking the IL-8/AR/MMPs signals either by anti-IL-8 neutralizing antibody, AR-siRNA, or MMPs inhibitors all partially reversed the infiltrating B cells capacity to increase the BCa cell invasion. The in vivo data from orthotopically xenografted BCa mouse model also confirmed that infiltrating B cells could increase BCa cell invasion via increasing AR signals. Together, these results demonstrate the key roles of B cells within the bladder tumor microenvironment that increase the BCa metastasis and may help us to develop the potential therapies via targeting these newly identified IL-8/AR/MMPs signals to better battle the BCa progression.
authors: Departments of Urology and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, USA.
authors: Zhenyu
authors: Z
authors: Ou
authors: Departments of Urology and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.|George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, USA.
authors: Yongjie
authors: Y
authors: Wang
authors: Departments of Urology and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors: Longfei
authors: L
authors: Liu
authors: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, USA.
authors: Lei
authors: L
authors: Li
authors: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, USA.
authors: Shuyuan
authors: S
authors: Yeh
authors: Departments of Urology and Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.
authors: Lin
authors: L
authors: Qi
authors: George Whipple Lab for Cancer Research, Departments of Pathology and Urology, University of Rochester Medical Center, Rochester, NY, USA.|Sex hormone Research Center, China Medical University/Hospital, Taichung, Taiwan.
authors: Chawnshang
authors: C
authors: Chang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C410798:AR protein, human; D016209:Interleukin-8; D061965:Matrix Metalloproteinase Inhibitors; D011944:Receptors, Androgen; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D020781:Matrix Metalloproteinase 1
keywords: B cell; androgen receptor; bladder cancer; tumor metastasis; tumor microenvironment