Kruse C A, Molleston M C, Parks E P, Schiltz P M, Kleinschmidt-DeMasters B K, Hickey W F
University of Colorado Health Sciences Center, Department of Surgery, Denver, USA.
J Neurooncol. 1994;22(3):191-200. doi: 10.1007/BF01052919.
A glioma cell line, CNS-1, was developed in the inbred Lewis rat to obtain a histocompatible astrocytoma cell line with infiltrative and growth patterns that more closely simulate those observed in human gliomas. Rats were given weekly intravenous injections for a six month period with N-nitroso-N-methylurea to produce neoplasm in the central nervous system. Intracranial tumor was isolated, enzymatically and mechanically digested, and placed into culture. The tumor cell line injected subcutaneously on the flanks of Lewis rats grew extensively in situ as cohesive tumor masses but did not metastasize. Intracranially, CNS-1 demonstrated single cell infiltration of paranchyma and leptomeningeal, perivascular, and periventricular spread with expansion of the tumor within choroid plexus stroma. CNS-1 cells titrated in right frontal brain of Lewis rats at 10(5), 5 x 10(5), 10(5), 5 x 10(4) cells per group had mean survival times ranging from 20.5 to 30.2 days. CNS-1 was immunoreactive for glial fibrillary acidic protein, S100 protein, vimentin, neural cell adhesion molecule, retinoic acid receptor alpha, intercellular adhesion molecule, and neuron specific enolase. The CNS-1 cells commonly had one or more trisomies of chromosomes 11, 13 or 18; losses, possibly random, of chromosomes (3, 5, 19, 30, X or Y) were noticed, and a marker chromosome made up of approximately 3 chromosomes was usual. Comparisons of CNS-1 to 9L gliosarcoma tumor were made. The glial CNS-1 tumor model provides an excellent system in which to investigate a variety of immunological therapeutic modalities. It spreads within brain in a less cohesive mass than 9L and is accepted without rejection in non-central nervous system sites by Lewis rats.
在近交系Lewis大鼠中建立了一种胶质瘤细胞系CNS-1,以获得一种组织相容性星形细胞瘤细胞系,其浸润和生长模式更接近人类胶质瘤中观察到的情况。给大鼠每周静脉注射N-亚硝基-N-甲基脲,持续6个月,以在中枢神经系统中产生肿瘤。分离出颅内肿瘤,进行酶解和机械消化,然后进行培养。将该肿瘤细胞系注射到Lewis大鼠的胁腹皮下,肿瘤在原位广泛生长,形成紧密的肿瘤块,但不发生转移。在颅内,CNS-1表现为实质的单细胞浸润以及软脑膜、血管周围和脑室周围扩散,并在脉络丛基质内肿瘤扩展。在Lewis大鼠的右额叶脑内,以每组10(5)、5×10(5)、10(5)、5×10(4)个细胞的剂量滴定CNS-1细胞,平均生存时间为20.5至30.2天。CNS-1对胶质纤维酸性蛋白、S100蛋白、波形蛋白、神经细胞黏附分子、视黄酸受体α、细胞间黏附分子和神经元特异性烯醇化酶具有免疫反应性。CNS-1细胞通常有11号、13号或18号染色体的一个或多个三体;注意到染色体(3、5、19、30、X或Y)可能随机丢失,并且通常有一条由大约3条染色体组成的标记染色体。对CNS-1和9L胶质肉瘤肿瘤进行了比较。胶质CNS-1肿瘤模型提供了一个极好的系统,可用于研究各种免疫治疗方法。它在脑内的扩散比9L更松散,并且在非中枢神经系统部位被Lewis大鼠接受而不被排斥。