title: B cells promote tumor progression via STAT3 regulated-angiogenesis.
abstract: The role of B cells in cancer and the underlying mechanisms remain to be further explored. Here, we show that tumor-associated B cells with activated STAT3 contribute to tumor development by promoting tumor angiogenesis. B cells with or without Stat3 have opposite effects on tumor growth and tumor angiogenesis in both B16 melanoma and Lewis Lung Cancer mouse models. Ex vivo angiogenesis assays show that B cell-mediated tumor angiogenesis is mainly dependent on the induction of pro-angiogenic gene expression, which requires Stat3 signaling in B cells. Furthermore, B cells with activated STAT3 are mainly found in or near tumor vasculature and correlate significantly with overall STAT3 activity in human tumors. Moreover, the density of B cells in human tumor tissues correlates significantly with expression levels of several STAT3-downstream pro-angiogenic genes, as well as the degree of tumor angiogenesis. Together, these findings define a novel role of B cells in promoting tumor progression through angiogenesis and identify STAT3 in B cells as potential therapeutic target for anti-angiogenesis therapy.
authors.affiliation: Department of Cancer Immunotherapeutics and Tumor Immunology, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Yang
authors.forename: Heehyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Sumanta
authors.initials: S
authors.lastname: Pal
authors.forename: Veronica
authors.initials: V
authors.lastname: Jove
authors.forename: Jiehui
authors.initials: J
authors.lastname: Deng
authors.forename: Wang
authors.initials: W
authors.lastname: Zhang
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
authors.forename: Mark
authors.initials: M
authors.lastname: Wakabayashi
authors.forename: Stephen
authors.initials: S
authors.lastname: Forman
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018450:Disease Progression; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology
chemical_list: D050796:STAT3 Transcription Factor