title: Trefoil Factor-3 (TFF3) Stimulates De Novo Angiogenesis in Mammary Carcinoma both Directly and Indirectly via IL-8/CXCR2.
abstract: Mammary carcinoma cells produce pro-angiogenic factors to stimulate angiogenesis and tumor growth. Trefoil factor-3 (TFF3) is an oncogene secreted from mammary carcinoma cells and associated with poor prognosis. Herein, we demonstrate that TFF3 produced in mammary carcinoma cells functions as a promoter of tumor angiogenesis. Forced expression of TFF3 in mammary carcinoma cells promoted proliferation, survival, invasion and in vitro tubule formation of human umbilical vein endothelial cells (HUVEC). MCF7-TFF3 cells with forced expression of TFF3 generated tumors with enhanced microvessel density as compared to tumors formed by vector control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA concordantly decreased the angiogenic behavior of HUVEC. Forced expression of TFF3 in mammary carcinoma cells stimulated IL-8 transcription and subsequently enhanced IL-8 expression in both mammary carcinoma cells and HUVEC. Depletion of IL-8 in mammary carcinoma cells with forced expression of TFF3, or antibody inhibition of IL-8, partially abrogated mammary carcinoma cell TFF3-stimulated HUVEC angiogenic behavior in vitro, as did inhibition of the IL-8 receptor, CXCR2. Depletion of STAT3 by siRNA in MCF-7 cells with forced expression of TFF3 partially diminished the angiogenic capability of TFF3 on stimulation of cellular processes of HUVEC. Exogenous recombinant hTFF3 also directly promoted the angiogenic behavior of HUVEC. Hence, TFF3 is a potent angiogenic factor and functions as a promoter of de novo angiogenesis in mammary carcinoma, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Wai-Hoe
authors.initials: WH
authors.lastname: Lau
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui, PR China.|Laboratory of Pathogenic Microbiology and Immunology, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Wang
authors.affiliation: Department of Pathology, Anhui Medical University, Hefei, Anhui, PR China.
authors.forename: ZhengSheng
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|National University Cancer Institute of Singapore, National Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D000071165:Trefoil Factor-3
chemical_list: D016209:Interleukin-8; D010455:Peptides; D023063:Receptors, Interleukin-8B; D050796:STAT3 Transcription Factor; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3