title: Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity.
abstract: Glioblastoma is the most malignant type of primary brain tumor that has been shown to contain a small population of cancer stem cells. Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies, it is not clear whether cancer stem cells are involved in invasiveness. In this study, we isolated tumor sphere-forming cells bearing cancer stem-like characteristics such as self-renewal, multipotency, drug-resistibility, and in vivo tumorigenicity, from the human glioblastoma cell line U251, under serum-free neural stem cell culture condition, and assessed their migratory and invasive ability. These cells showed enhanced migratory and invasive ability on both Matrigel and organotypic brain slices compared to parental U251 cells. The expression of matrix metalloproteinase (MMP)-13 was specifically expressed in tumor sphere-forming cells derived from U251 and primary human glioma cells. Knockdown of MMP-13 expression by shRNA suppressed the migration and invasion of these cells. The results suggest that the highly invasive potential of cancer stem cells depends on MMP-13 enzymatic activity, thus MMP-13 might be a potential therapeutic target for glioblastomas.
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inoue
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Harada
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Shiro
authors.initials: S
authors.lastname: Ohue
authors.forename: Kana
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hajime
authors.initials: H
authors.lastname: Yano
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002469:Cell Separation; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D009924:Organ Culture Techniques; D051381:Rats; D014183:Transplantation, Heterologous
chemical_list: D053509:Matrix Metalloproteinase 13