Cancer stem-like cells of glioblastoma characteristically express MMP-13 and display highly invasive activity.
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.
Inoue
Akihiro
A
Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
Takahashi
Hisaaki
H
Harada
Hironobu
H
Kohno
Shohei
S
Ohue
Shiro
S
Kobayashi
Kana
K
Yano
Hajime
H
Tanaka
Junya
J
Ohnishi
Takanori
T
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
D053509:Matrix Metalloproteinase 13