Endogenous growth inhibition of angiogenesis in brain tumors

Abstract

The growth inhibition of remote metastases by a primary tumor is known as endogenous growth inhibition leading to tumor dormancy. Such a phenotype has not been described in primary malignant gliomas. However, although glioma cells have frequently spread to other parts of the brain at the time of diagnosis, formation of solid secondary tumors is uncommon. We hypothesize that a dormant population of distant glioma cells exist. The purpose of this study was to investigate whether primary gliomas could inhibit secondary tumor formation. Subcutaneous tumors from human gliomas were grown as xenografts in Swiss nude mice. At a tumor size of at least one cm(3), the same amount of cells was injected into the contralateral flank or into the right cerebral hemisphere. Control mice without a primary tumor were injected with tumor cells either into the right flank, the right hemisphere, or bilaterally subcutaneously. Only one of 18 human gliomas demonstrated inhibition at the subcutaneous and intracerebral secondary implantation sites. Growth inhibition of the secondary tumors was accompanied by a significant reduction in microvessel density, upregulation of vascular endothelial growth factor mRNA and downregulation of basic fibroblast growth factor mRNA. Therefore, endogenous inhibition of secondary tumors may represent a rare phenotype in malignant glioma.

Proton MR Spectroscopy of Neural Stem Cells: Does the Proton-NMR Peak at 1.28 ppm Function As a Biomarker for Cell Type or State?

“…Fetal cortical NSCs were isolated from embryonic C57/BL6 mouse brain at embryonic day 14 (E14) and cultured in neurospheres as described in Milosevic et al 19 These neurosphere cultures were highly enriched NSC cultures with 91.4 AE 9.2% of nestin þ NSCs (n ¼ 5). The protocol used for mixed primary neural cultures containing both glial and neuronal cells was reported in Freudenberg et al 20 Pure astrocytic cultures were prepared according to Song et al, 21 embryonic stem (ES) cells and ES-cell derived NSCs according to Kawasaki et al, 22 and induced pluripotent stem (iPS) cell-derived NSCs and embryonic fibroblasts as described in Kim et al 23 MN9D cells were grown according to Heller et al 24 and melanoma and glioma cell lines according to Kirsch et al 25 and Uo et al, 26 respectively. Note that all cells are of murine origin.…”