Pedersen P H, Rucklidge G J, Mørk S J, Terzis A J, Engebraaten O, Lund-Johansen M, Backlund E O, Laerum O D, Bjerkvig R
Gade Institute Department of Pathology, University of Bergen, Norway.
J Natl Cancer Inst. 1994 Nov 2;86(21):1593-9. doi: 10.1093/jnci/86.21.1593.
Primary brain tumors are characterized by an extensive infiltrative growth into the surrounding brain tissue. This process is confined to the central nervous system, and tumor cell metastasis to other organs is rare. However, other tumors of non-neural origin may frequently metastasize to the central nervous system.
The purpose of the present study was to examine the invasive behavior of different glioma cells into tissues of neural (brain aggregates) as well as non-neural origin (leptomeningeal tissue). Using the same target tissues, the invasive characteristics of two neural metastatic tumors (one malignant melanoma and one small-cell lung carcinoma) were also studied. This direct comparison of the invasive behavior between tumors of neural and non-neural origin provides valuable information regarding the mechanisms of glioma cell dissemination in the central nervous system.
The in vitro invasive behavior of human tumors of the central nervous system into human leptomeningeal tissue as well as into normal rat brain tissue was studied. For this purpose, a co-culture system consisting of tumor biopsy specimens, human leptomeningeal cell aggregates, and brain cell aggregates was established. Three glioblastomas, one oligodendroglioma, one meningioma, one small-cell lung carcinoma, and one malignant melanoma were studied.
In co-cultures of gliomas and leptomeningeal cell aggregates, a well-defined border between the two tissues was observed. The brain cell aggregates, in contrast, were consistently invaded by the glioma cells. The brain metastases showed a different invasion pattern. The metastatic cells invaded and progressively destroyed leptomeningeal cell aggregates, whereas they did not invade the brain cell aggregates. Upon confrontation of the leptomeningeal tissue with the meningioma, a fusion of the two tissues was observed. Immunostaining of the leptomeningeal tissue showed a strong expression of the basement membrane components fibronectin, collagen type IV, and laminin with no expression of glial fibrillary acidic protein, neuron-specific enolase, or S-100 protein.
The present study indicates that there may be important biologic differences between the invasive behavior of gliomas and non-neuroepithelial tumors. Our co-culture experiments suggest that leptomeningeal cells and associated acellular components may constitute a barrier against glioma cell invasion. However, this barrier may not be functional for metastatic tumors to the brain. The presence of glioma cells within the leptomeninges should not necessarily be taken as evidence of aggressive growth or as an indicator of malignancy.
原发性脑肿瘤的特征是广泛浸润周围脑组织。此过程局限于中枢神经系统，肿瘤细胞转移至其他器官的情况罕见。然而，其他非神经源性肿瘤可能经常转移至中枢神经系统。
本研究的目的是检测不同胶质瘤细胞对神经组织（脑聚集体）以及非神经源性组织（软脑膜组织）的侵袭行为。使用相同的靶组织，还研究了两种神经转移性肿瘤（一种恶性黑色素瘤和一种小细胞肺癌）的侵袭特征。这种对神经源性和非神经源性肿瘤侵袭行为的直接比较为胶质瘤细胞在中枢神经系统中扩散的机制提供了有价值的信息。
研究了人类中枢神经系统肿瘤对人软脑膜组织以及正常大鼠脑组织的体外侵袭行为。为此，建立了一个由肿瘤活检标本、人软脑膜细胞聚集体和脑细胞聚集体组成的共培养系统。研究了3例胶质母细胞瘤、1例少突胶质细胞瘤、1例脑膜瘤、1例小细胞肺癌和1例恶性黑色素瘤。
在胶质瘤与软脑膜细胞聚集体的共培养中，观察到两种组织之间有明确的边界。相比之下，胶质瘤细胞持续侵袭脑细胞聚集体。脑转移瘤表现出不同的侵袭模式。转移细胞侵袭并逐渐破坏软脑膜细胞聚集体，而它们不侵袭脑细胞聚集体。当软脑膜组织与脑膜瘤接触时，观察到两种组织融合。软脑膜组织的免疫染色显示基底膜成分纤连蛋白、IV型胶原和层粘连蛋白强烈表达，而胶质纤维酸性蛋白、神经元特异性烯醇化酶或S-100蛋白无表达。
本研究表明，胶质瘤和非神经上皮性肿瘤的侵袭行为可能存在重要的生物学差异。我们的共培养实验表明，软脑膜细胞和相关的无细胞成分可能构成胶质瘤细胞侵袭的屏障。然而，这种屏障对脑转移性肿瘤可能不起作用。软脑膜内存在胶质瘤细胞不一定应被视为侵袭性生长的证据或恶性程度的指标。
