title: Metallothinein 1E Enhances Glioma Invasion through Modulation Matrix Metalloproteinases-2 and 9 in U87MG Mouse Brain Tumor Model.
abstract: Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasionin vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.
authors.affiliation: Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Hur
authors.affiliation: Brain Tumor Clinic and Gamma Knife Center and Brain Tumor Research Laboratory, and Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: Hyang-Hwa
authors.initials: HH
authors.lastname: Ryu
authors.affiliation: Brain Tumor Clinic and Gamma Knife Center and Brain Tumor Research Laboratory, and Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: In Young
authors.initials: IY
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: Woo-Youl
authors.initials: WY
authors.lastname: Jang
authors.affiliation: Department of Neurosurgery, Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.; Brain Tumor Clinic and Gamma Knife Center and Brain Tumor Research Laboratory, and Chonnam National University Research Institute of Medical Sciences, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Jung
keywords: Brain tumor model; Invasion; MMP-2; MMP-9; Malignant glioma; Metallothionein 1E