gms | German Medical Science

Objective: As early as in 1858 Rudolf Virchow assumed that cancer arises from embryo-like cells. In this later extended concept (embryonal rest theory) aggressive cancer cells share histological similarities to embryonic stem cells. As differentiated cells acquire embryonic pluripotency and self-renewal by transfection with transcription factors like Oct4, Sox2, Nanog, Klf4 and c-Myc, we investigated their occurrence and frequency in human astrocytomas and glioma cell lines.

Method: Gene transcription was analyzed by quantitative RT-PCR and protein expression by immunohistochemistry. Positive cells were counted by an unbiased person for single or multiple expressions.

Results: Tumor samples showed a moderate to high mRNA expression of all transcription factors, with Sox2 and c-Myc as most pronounced. Among astrocytomas of different WHO grades, expression of c-Myc, Oct 4 and Sox2 increases with malignancy. As in solid tumors, Sox2 and c-Myc were most abundantly expressed also in glioblastoma cells lines, Nanog and Klf4 were expressed only at low levels. Co-staining with glial-specific markers proved an expression of all transcription factors in astrocytoma cells in situ and in vitro. However, in solid tumors expression was restricted to a subpopulation of cells ranging from 5-10% for all factors. Furthermore, cells positive for one transcription factor frequently co-stained for another factor, but single positive cells were also found in different proportions.

Conclusions: We conclude that human astrocytomas contain a low, but constant proportion of cells expressing embryonic and/or neural stem cell factors, some increasing with malignancy. Investigations are undergoing to relate them to further characteristics, e. g. receptors for growth and chemotaxis factors.