title: Gene silencing of c-Met leads to brain metastasis inhibitory effects.
abstract: An unfortunate consequence of improvements in the treatments of advanced primary cancers is the concurrent increase of metastatic brain tumors. Despite of unfavorable clinical prognosis, radiation therapy is still the only viable treatment option for brain metastases. Expression of c-Met induces cell migration and invasion in many cancers, which are indispensable steps for metastasis. Accordingly, we examined the effects of gene silencing of c-Met on brain metastasis to evaluate the possibility of c-Met as a potential target. MDA-MB-435 cells were transfected with c-Met targeting short hairpin RNAs (shRNAs). Effects of c-Met shRNAs on the expression of epithelial mesenchymal transition (EMT) related proteins, in vitro migration, and in vivo brain metastasis were examined. Expression of mesenchymal markers and in vitro migration of MDA-MB-435 cells were significantly inhibited by introduction of c-Met shRNAs. When c-Met-silenced MDA-MB-435 cells were stereotactically implanted into the brains of immune-compromised mice or injected into the right internal carotid arteries, c-Met-silenced MDA-MB-435 cells produced significantly smaller tumor masses or survival time was significantly prolonged, respectively, compared with MDA-MB-435 cells transfected with control shRNA. The data reveal the novel function of c-Met in the process of brain metastasis and its potential as a preventive and/or therapeutic target in this disease.
authors.affiliation: Department of Neurosurgery Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul, 135-710, South Korea.
authors.forename: Se Jeong
authors.initials: SJ
authors.lastname: Lee
authors.forename: Ho Jun
authors.initials: HJ
authors.lastname: Seol
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Won Young
authors.initials: WY
authors.lastname: Kang
authors.forename: Bong Gu
authors.initials: BG
authors.lastname: Kang
authors.forename: Juyoun
authors.initials: J
authors.lastname: Jin
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Jo
authors.forename: Younggeon
authors.initials: Y
authors.lastname: Jin
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Lee
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D019859:Proto-Oncogene Proteins c-met