Kotitschke K, Tonn J C, Goldbrunner R, Bogdahn U, Haase A
Institute of Physics, University of Würzburg, Germany.
J Magn Reson B. 1995 Oct;109(1):39-43. doi: 10.1006/jmrb.1995.1144.
Three-dimensional spherical aggregates of cells, grown from a permanent human malignant glioma cell line (multicellular GaMG spheroids) and from a human glioma biopsy (fragment spheroids), were investigated by 1H NMR spectroscopy. In addition, 1H NMR spectra of biopsy specimens immediately after explantation and of cell monolayers from primary passage and passage 5 were acquired and compared to those of fragment spheroids. By allowing tumor cells to grow in a three-dimensional arrangement, many biological characteristics of the original tumor in vivo are preserved. A technical procedure was established, indicating that spheroids are particularly suited for NMR spectroscopic studies. Well-resolved proton NMR spectra were obtained from homogeneously reaggregated as well as from fragment spheroids which were immobilized in agar. We found that fragment spheroids closely resemble characteristic spectral patterns of the corresponding tumor tissue in vitro, thus making such tissue available for 1H NMR spectroscopic measurements under easy to standardize tissue-culture conditions. Furthermore, the effect of altering glucose supply on metabolism and growth was studied with multicellular GaMG spheroids. The spectroscopic differences found between cell suspensions and multicellular spheroids indicate that GaMG spheroids produce large amounts of lactate and that they can adapt their metabolism depending on glucose supply similar to tumors in vivo.
利用1H核磁共振波谱法对源自人恶性胶质瘤永久细胞系（多细胞GaMG球体）和人胶质瘤活检样本（碎片球体）的三维球形细胞聚集体进行了研究。此外，还获取了活检样本刚取出时、原代传代和第5代传代细胞单层的1H核磁共振波谱，并与碎片球体的波谱进行了比较。通过让肿瘤细胞以三维方式生长，体内原始肿瘤的许多生物学特性得以保留。建立了一种技术程序，表明球体特别适合核磁共振波谱研究。从均匀重新聚集的以及固定在琼脂中的碎片球体中获得了分辨率良好的质子核磁共振波谱。我们发现，碎片球体在体外与相应肿瘤组织的特征光谱模式非常相似，从而使得这种组织能够在易于标准化的组织培养条件下进行1H核磁共振波谱测量。此外，还利用多细胞GaMG球体研究了改变葡萄糖供应对代谢和生长的影响。细胞悬液和多细胞球体之间发现的光谱差异表明，GaMG球体产生大量乳酸，并且它们能够像体内肿瘤一样根据葡萄糖供应来调节自身代谢。
