Akbasak A, Toevs C C, Laske D W
Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
J Neurooncol. 1996 Jan;27(1):23-30. doi: 10.1007/BF00146080.
Transplantation of human cancers into immunologically deficient mice is widely used to study potential therapeutic interventions in vivo. For brain tumor research, however, several factors limit more widespread application of this animal model. First, only a minority of human glioma-derived cell lines are tumorigenic in nude mice. In addition, even for tumorigenic cell lines, tumor take is variable and growth is often slow for tumors derived from cell inoculums. Reconstituted components of tumor basement membrane (matrigel) have been found to improve the growth in nude mice of several types of human tumors originating outside the central nervous system when premixed with the tumor cells before subcutaneous inoculation. We investigated the ability of matrigel to enhance the growth in nude mice of tumors derived from the human glioma cell lines U-251 MG, U-373 MG, SNB-78 and SNB-101. Athymic nude mice (NIH Swiss background, nu/nu genotype) were inoculated subcutaneously with 1.0 x 10(6) tumor cells alone or after premixing with an equal volume of liquid matrigel. U-251 and U-373 cells were tumorigenic, with palpable tumors present by about 2 to 3 weeks. Co-injection of these cell lines with matrigel resulted in higher tumor-take rates, from 6/10 to 8/8 animals for U-251 at 60 days, and from 9/12 to 11/11 animals for U-373 at 60 days. Matrigel also enhanced tumor growth, with tumors at 45 days significantly larger than those formed in the absence of matrigel, for both cell lines (p < 0.01). SNB-78 and SNB-101 cells did not give rise to progressively enlarging solid tumors with or without matrigel. Matrigel enhances the growth of tumorigenic human gliomas in athymic nude mice. This technique provides a model with more consistent tumor take and more rapid growth kinetics for human glioma cell lines that are tumorigenic in nude mice.
将人类癌症移植到免疫缺陷小鼠体内被广泛用于研究体内潜在的治疗干预措施。然而,对于脑肿瘤研究,有几个因素限制了这种动物模型更广泛的应用。首先,只有少数源自人类胶质瘤的细胞系在裸鼠中具有致瘤性。此外,即使对于具有致瘤性的细胞系,肿瘤接种成功率也存在差异,并且源自细胞接种物的肿瘤生长通常缓慢。已发现肿瘤基底膜的重组成分(基质胶)在皮下接种前与肿瘤细胞预混合时,可改善几种源自中枢神经系统以外的人类肿瘤在裸鼠中的生长。我们研究了基质胶增强源自人类胶质瘤细胞系U - 251 MG、U - 373 MG、SNB - 78和SNB - 101的肿瘤在裸鼠中生长的能力。无胸腺裸鼠(NIH瑞士背景,nu/nu基因型)皮下接种1.0×10(6)个肿瘤细胞,或在与等体积的液体基质胶预混合后接种。U - 251和U - 373细胞具有致瘤性,约2至3周后可触及肿瘤。这些细胞系与基质胶共同注射导致更高的肿瘤接种成功率,U - 251在60天时从6/10只动物增加到8/8只,U - 373在60天时从9/12只动物增加到11/11只。基质胶还促进了肿瘤生长,对于这两种细胞系,45天时的肿瘤明显大于未使用基质胶形成的肿瘤(p < 0.01)。无论有无基质胶,SNB - 78和SNB - 101细胞都不会产生逐渐增大的实体瘤。基质胶可增强无胸腺裸鼠中具有致瘤性的人类胶质瘤的生长。该技术为在裸鼠中具有致瘤性的人类胶质瘤细胞系提供了一个肿瘤接种成功率更一致且生长动力学更快的模型。