Reconstituted basement membrane (matrigel) enhances the growth of human glioma cell lines in nude mice

Abstract

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.