title: Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer.
abstract: Aggressive cancer phenotypes are a manifestation of many different genetic alterations that promote rapid proliferation and metastasis. In this study, we show that stable overexpression of Twist in a breast cancer cell line, MCF-7, altered its morphology to a fibroblastic-like phenotype, which exhibited protein markers representative of a mesenchymal transformation. In addition, it was observed that MCF-7/Twist cells had increased vascular endothelial growth factor (VEGF) synthesis when compared with empty vector control cells. The functional changes induced by VEGF in vivo were analyzed by functional magnetic resonance imaging (MRI) of MCF-7/Twist-xenografted tumors. MRI showed that MCF-7/Twist tumors exhibited higher vascular volume and vascular permeability in vivo than the MCF-7/vector control xenografts. Moreover, elevated expression of Twist in breast tumor samples obtained from patients correlated strongly with high-grade invasive carcinomas and with chromosome instability, particularly gains of chromosomes 1 and 7. Taken together, these results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an aggressive breast cancer phenotype.
authors.affiliation: Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Mironchik
authors.forename: Paul T
authors.initials: PT
authors.lastname: Winnard
authors.forename: Farhad
authors.initials: F
authors.lastname: Vesuna
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kato
authors.forename: Flonne
authors.initials: F
authors.lastname: Wildes
authors.forename: Arvind P
authors.initials: AP
authors.lastname: Pathak
authors.forename: Scott
authors.initials: S
authors.lastname: Kominsky
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
authors.forename: Zaver
authors.initials: Z
authors.lastname: Bhujwalla
authors.forename: Paul
authors.initials: P
authors.lastname: Van Diest
authors.forename: Horst
authors.initials: H
authors.lastname: Burger
authors.forename: Carlotta
authors.initials: C
authors.lastname: Glackin
authors.forename: Venu
authors.initials: V
authors.lastname: Raman
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D043171:Chromosomal Instability; D057167:Claudins; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis*; D015533:Transcriptional Activation; D014183:Transplantation, Heterologous; D051879:Twist-Related Protein 1 / Q000096:biosynthesis*
chemical_list: C473255:CLDN7 protein, human; D057167:Claudins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1