© 2005 by the Society forNeuro-Oncology
Patient tumor EGFR and PDGFRA gene amplificationsretained in an invasive intracranial xenograft model of glioblastomamultiforme
Departments of Laboratory Medicine and Pathology(C.G., A.S., M.A.S., C.D.J.), Oncology (J.N.S., E.G.,B.L.C.), and Neurology (J.H.U.), Mayo Clinic andFoundation, Rochester, MN 55905, USA
2 Address correspondence to C. David James, Division of Experimental Pathology,Mayo Clinic, 200 First Street SW, Hilton Building, Room 820-D, Rochester, MN55905, USA(james.david{at}mayo.edu).
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We have previously described a panel of serially transplantableglioblastoma multiforme xenograft lines established by direct subcutaneousinjection of patient tumor tissue in the flanks of nude mice. Here we reportthe characterization of four of these lines with respect to theirhistopathologic, genetic, and growth properties followingheterotopic-to-orthotopic (flank-to-intracranial) transfer. Cells fromshort-term cultures, established from excised flank xenografts, were harvestedand injected into the brains of nude mice (106 cells perinjection). The intracranial tumors generated from these injections were allhighly mitotic as well as highly invasive, but they lacked necrotic featuresin most instances and failed to show endothelial cell proliferation in allinstances. For mice receiving injections from a common explant culture, tumorintracranial growth rate was consistent, as indicated by relatively narrowranges in survival time. In contrast to the loss of epidermal growth factorreceptor gene (EGFR) amplification in cell culture, high-levelamplification and overexpression of EGFR were retained inintracranial tumors established from two EGFR-amplified flank tumors.A third intracranial tumor retained patient tumor amplification and high-levelexpression of platelet-derived growth factor receptor alpha gene. Because theheterotopic-to-orthotopic transfer and propagation of glioblastoma multiformepreserves the receptor tyrosine kinase (RTK) gene amplification of patienttumors, this approach should facilitate investigations for determining theextent to which RTK amplification status influences tumor response toRTK-directed therapies. The fact that such studies were carried out by usingan invasive tumor model in an anatomically appropriate context should ensure arigorous preclinical assessment of agent efficacy.
Received September 3, 2004; Accepted December 1, 2004
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