RECONSTITUTED BASEMENT-MEMBRANE (MATRIGEL) ENHANCES THE GROWTH OF HUMAN GLIOMA CELL-LINES IN NUDE-MICE

Transplantation of human cancers into immunologically deficient mice i s widely used to study potential therapeutic interventions in vivo. Fo r brain tumor research, however, several factors limit more widespread application of this animal model. First, only a minority of human gli oma-derived cell lines are tumorigenic in nude mice. In addition, even for tumorigenic cell lines, tumor take is variable and growth is ofte n slow for tumors derived from cell inoculums. Reconstituted component s of tumor basement membrane (matrigel) have been found to improve the growth in nude mice of several types of human tumors originating outs ide the central nervous system when premixed with the tumor cells befo re subcutaneous inoculation. We investigated the ability of matrigel t o enhance the growth in nude mice of tumors derived from the human gli oma cell lines U-251 MG, U-373 MG, SNB-78 and SNB-101. Athymic nude mi ce (NIH Swiss background, nu/nu genotype) were inoculated subcutaneous ly 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, wi th palpable tumors present by about 2 to 3 weeks. Co-injection of thes e 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 animal s for U-373 at 60 days. Matrigel also enhanced tumor growth, with tumo rs 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 di d not give rise to progressively enlarging solid tumors with or withou t matrigel. Matrigel enhances the growth of tumorigenic human gliomas in athymic nude mice. This technique provides a model with more consis tent tumor take and more rapid growth kinetics for human glioma cell l ines that are tumorigenic in nude mice.