Artikel
The neural cell adhesion molecule L1CAM confers chemoresistance to human glioblastoma progenitor cells
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Veröffentlicht: | 28. April 2011 |
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Gliederung
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Objective: Glioblastomas are highly malignant brain tumors marked by poor prognosis and unsatisfactory response to treatments such as radio- and chemotherapy. The neural cell adhesion molecule L1CAM is expressed in various types of cancers including glioblastoma and has been demonstrated to facilitate metastasis and progression. Our current study introduces a potential role for L1CAM in chemoresistance and glioblastoma stem cell development.
Results: We demonstrated by qRT-PCR and FACS, that L1CAM is expressed in glioblastomas and – as shown for T98G and 27/07 glioblastoma cells – can be induced by TGF-ß1 (qRT-PCR, Western Blot). Transfection with L1CAM (efficiency proven by qRT-PCR and Western Blot) of both human primary and regular glioblastoma cell lines, as well as glioblastoma progenitor spheroids yielded in higher chemoresistance after Temozolomide treatment - assessed via caspase-3/-7-assay. In addition, as discovered in scratch-assays, L1CAM enhanced migration of the named cell types. Vice versa, transfection with L1CAM siRNA clearly diminished chemoresistance and migration. Interestingly, we detected by qRT-PCR that during differentiation of glioblastoma progenitor spheroids, L1CAM as well as TGF-ß1 expression increases considerably.
Conclusions: L1CAM expression in several glioblastoma cell lines is inducible by TGF-ß1, a common and highly expressed cytokine in these highly malignant brain tumors. L1CAM enhances migration and chemoresistance in glioblastoma cell lines, primary cultures and glioblastoma progenitor cells. Therefore, L1CAM could play a role in glioblastomas’ bad response to chemotherapy.