4.3 Article

Microtubule-Severing ATPase Spastin in Glioblastoma: Increased Expression in Human Glioblastoma Cell Lines and Inverse Roles in Cell Motility and Proliferation

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出版社

OXFORD UNIV PRESS INC
DOI: 10.1097/NEN.0b013e31822c256d

关键词

Astrocyte; Brain tumor; Cell motility; Glioblastoma; Glioma; Microtubule severing; Spastin

资金

  1. Czech Science Foundation [P302/10/1701, 204/09/1777, 204/09/H084]
  2. Grant Agency ASCR [KAN200520701]
  3. Ministry of Education, Youth and Sports of the Czech Republic [LC545]
  4. institutional research [AVOZ 50520514, AVOZ 50110509]
  5. National Institutes of Health [R01 NS066942A, RO1 NS28785]
  6. ALS Therapy Alliance
  7. National Science Foundation [0841245]
  8. State of Pennsylvania Tobacco Settlement Funds
  9. St. Christopher's Foundation for Children to Christos D. Katsetos [203]

向作者/读者索取更多资源

We studied the expression and distribution of the microtubule-severing enzyme spastin in 3 human glioblastoma cell lines (U87MG, U138MG, and T98G) and in clinical tissue samples representative of all grades of diffuse astrocytic gliomas (n = 45). In adult human brains, spastin was distributed predominantly in neurons and neuropil puncta and, to a lesser extent, in glia. Compared with normal mature brain tissues, spastin expression and cellular distribution were increased in neoplastic glial phenotypes, especially in glioblastoma (p < 0.05 vs low-grade diffuse astrocytomas). Overlapping punctate and diffuse patterns of localization were identified in tumor cells in tissues and in interphase and mitotic cells of glioblastoma cell lines. There was enrichment of spastin in the leading edges of cells in T98G glioblastoma cell cultures and in neoplastic cell populations in tumor specimens. Real-time polymerase chain reaction and immunoblotting experiments revealed greater levels of spastin messenger RNA and protein expression in the glioblastoma cell lines versus normal human astrocytes. Functional experiments indicated that spastin depletion resulted in reduced cell motility and higher cell proliferation of T98G cells. To our knowledge, this is the first report of spastin involvement in cell motility. Collectively, our results indicate that spastin expression in glioblastomas might be linked to tumor cell motility, migration, and invasion.

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