title: Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells.
abstract: Brain metastasis is a major cause of morbidity and mortality in patients with breast cancer. Our previous studies indicated that Stat3 plays an important role in brain metastasis. Here, we present evidence that Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells. Furthermore, inhibition of Stat3 by WP1066 decreased the incidence of brain metastases and increased survival in a preclinical model of breast cancer brain metastasis. WP1066 inhibited Stat3 activation in tumor-associated endothelial cells, reducing their infiltration and angiogenesis. WP1066 also inhibited breast cancer cell invasion. Our results indicate that WP1066 can inhibit tumor angiogenesis and brain metastasis mediated by Stat3 in endothelial and tumor cells.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hsueh-Te
authors.initials: HT
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ping-Chieh
authors.initials: PC
authors.lastname: Chou
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Aidong
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Aldape
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Priebe
authors.affiliation: Division of Cardiology and McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Cam
authors.initials: C
authors.lastname: Patterson
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.affiliation: Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.|Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
authors.forename: Suyun
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays
chemical_list: D011725:Pyridines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020032:Tyrphostins; C519885:WP1066; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Stat3; Stat3 inhibitor; VEGFR2; brain endothelial cells; brain metastasis