In vivo establishment of T98G human glioblastoma

Human derived T98G glioblastoma has long been utilized as an in vitro model for. epidermal growth factor receptor (EGFR)-mediated growth regulation. R ecently, T98G has been employed to develop new types of therapy directed at limiting EGFR expression such as by administration of antisense oligonucle otides directed against EGFR encoding mRNA. A major limitation to extending this model for in vivo application is that T98G implanted s.c. or intracer ebrally has been reported riot to grow in nude mice. In an effort to extend this model to permit in vivo studies, we evaluated the use of Matrigel and orthotopic (intracranial) implantation techniques. When equal volumes of M atrigel were mixed with T98G cell suspensions, rumors developed at both fla nk and orthotopic locations. Four groups of nude mice were inoculated into the flanks with either 10(5), 10(6), 4 x 10(6) or 10(7) T98G cells in a 150 mu l total volume with Matrigel. In 1/5, 3/5, 1/5 and 1/3 mice receiving 1 0(5), 10(6), 4 x 10(6) and 10(7) cells, respectively tumors developed 11, 1 5, 15 and 15 weeks, respectively, following inoculation. Out of 4 mice inoc ulated orthotopically (intracranially into the frontal lobe) with only 4 x 10(4) cells and Matrigel, 2 developed tumors. However; all mice (4/4) inocu lated orthotopically with 4 x 10(5) cells in a 10 mu l total volume with Ma trigel developed tumors. Two were identified histologically following a sch eduled sacrifice at 36 and 60 days and two more at 103 and 118 days after s acrifice following abnormal behavior: The best tumor establishment efficacy combined orthotopic implantation of 4 x 10(5) T98G cells with Matrigel. Th ese techniques permit the use of T98G glioblastoma as an in vivo model for new forms of therapy. (C)1999 Prous Science. All rights reserved.