Role of sonic hedgehog signaling in migration of cell lines established from CD133-positive malignant glioma cells

Autor: Shunji Yunoue, Hiroyuki Uchida, Hirofumi Hirano, Kazunori Arita, Hiroshi Tokimura, Hajime Yonezawa, Yoshinari Shinsato, Ryosuke Hanaya, Hiroto Kawano
Rok vydání: 2011
Předmět:
Zdroj: Journal of Neuro-Oncology. 104:697-704
ISSN: 1573-7373
0167-594X
Popis: The sonic hedgehog (SHH) signaling pathway is essential for normal development and embryogenic morphogenesis. In malignant neoplasms its inappropriate activation correlates with tumorigenesis, proliferation, and migration. However, the role of SHH in infiltrative growth of glioblastoma remains to be elucidated. CD133 is a marker of tumor stem cells in glioblastoma, which are thought to play important roles in tumorigenesis, drug resistance, and tumor recurrence. We investigated the role of the SHH signaling pathway in migration of glioblastoma cell lines derived from CD133-positive cells. Two cell lines, GBM1 and GBM2, were established from CD133-positive cells sorted on an automagnetic cell separator from dispersed human glioblastoma cells. Both cell lines exhibited sphere-like growth in serum-free medium containing growth factor. Expression of patched (PTCH)-, a receptor of SHH, of smoothened (SMO)-, a 7 transmembrane receptor, and of GLI1- and GLI2, PTCH cascade signal proteins, was evaluated by reverse-transcription polymerase chain reaction (RT-PCR). The effects of recombinant SHH in the medium, and of knockdown of SMO-, GLI1- or GLI2 messenger RNA (mRNA) on the migratory ability of neoplastic cells were evaluated by scratch assays. RT-PCR revealed the presence of PTCH-, SMO-, GLI1-, and GLI2 mRNA in these cells. Their migratory ability was significantly enhanced (P
Databáze: OpenAIRE