Immortalized cells and one oncogene in malignant transformation: old insights on new explanation

<p>Abstract</p> <p>Background</p> <p>Nearly thirty years ago, it was first shown that malignant transformation with single oncogene necessarily requires the immortal state of the cell. From that time this thesis for the cells of human origin was not disproved. The basic point which we want to focus on by this short communication is the correct interpretation of the results obtained on the widely used human embryonic kidney 293 (HEK293) cells.</p> <p>Results</p> <p>Intensive literature analysis revealed an increasing number of recent studies discovering new oncogenes with non-overlapping functions. Since the 1970s, dozens of oncogenes have been identified in human cancer. Cultured cell lines are often used as model systems in these experiments. In some investigations the results obtained on such cells are interpreted by the authors as a malignant transformation of normal animal or even normal human cells (as for example with HEK293 cells). However, when a cell line gains the ability to undergo continuous cell division, the cells are not normal any more, they are immortalized cells. Nevertheless, the authors consider these cells as normal human ones, what is basically incorrect. Moreover, it was early demonstrated that the widely used human embryonic kidney 293 (HEK293) cells have a relationship to neurons.</p> <p>Conclusions</p> <p>Thus, the experiments with established cell lines reinforce the notion that immortality is an essential requirement for malignant transformation that cooperates with other oncogenic changes to program the neoplastic state and substances under such investigation should be interpreted as factors which do not malignantly transform normal cells alone, but possess the ability to enhance the tumorigenic potential of already immortalized cells.</p

New Experimental Model of Brain Tumors in Brains of Adult Immunocompetent Rats

Aims: Xenograft models, namely heterotransplantation of human cancer cells or tumor biopsies into immunodeficient rodents are the major preclinical approach for the development of novel cancer therapeutics. However, in these models the animals must be used only after the severe systemic immune suppression in order to ensure graft survival. Thus, additional new human brain tumor models without immune suppression of the recipient rodent may be required. Place and Duration of Study: Laboratory of Immunochemistry, V.P. Serbsky National Research Centre for Social and Forensic Psychiatry and Department of Nanobiotechnology, N.I. Pirogov Russian State Medical University and Department of Biosynthesis of Nucleic Acids, Institute of Molecular Biology and Genetics between June 2009 and July 2010. Methodology: Brain tumor modeling was performed by intracerebral stereotactic implantation of cells to the healthy adult rats without any artificial immunodepression. Cells were implanted to the striatum region of ketamine-anesthetized rats at specific coordinates according to Swanson's rat brain atlas. Tumor growth was monitored weekly via registration of neurological signs and in vivo Bruker MRI system. Results: On the 21st day after implantation of C6 glioma, U251 or 293_CHI3L1 cells severe neurological deficit appeared in rats. Huge intracerebral tumors were found in each animal under investigation while no tumor growth was observed for at least 8 weeks in rats injected with empty vector-transfected 293 cells. Tumors contained the dense superficial cell layer and prominent lobules with central newly ingrowing blood vessels. Histological assay revealed displacement of median cerebral structures and hydrocephalus in contralateral hemisphere. All tumors were surrounded by numerous GFAP-positive reactive astrocytes. Conclusion: Positive results with transplantation of 293_CHI3L1 cells into adult rat brains without any immunosupression show the validity of this animal model. In all experiments such implantations provoked malignant tumor formation while there were no visible tumors in control rats. We believe this to be the first animal model of human brain tumor that displays the possibility to study various biologic features of and host therapeutic response to brain tumor in an immunocompetent host