U118 Xenograft Model

U118 Brain Cancer Xenograft Model

Glioblastoma, or glioblastoma multiforme (GBM), is an aggressive brain cancer with symptoms including nausea, personality changes, headaches, or stroke-like symptoms. Causes of glioblastoma remain unclear, although rare genetic disorders can be risk factors. Usual onset is above 64 years of age. Temozolomide and steroids are common drug treatments; surgery and radiation are also used. The U118 cell line was derived from a 50 yo Caucasian male diagnosed with astrocytoma. The U118 model has been used in many glioblastoma research studies. A 2008 Journal of Translational Medicine article (Xie et al.) used various glioblastoma cell lines, including U118, in order to generate invasive orthotopic xenografts optimized for real-time ultrasounds of tumors so that anti-neoplastic drugs such as 17AAG may be evaluated. The group used experimental lung metastasis (ELM) assays in select for the most metastatic/aggressive cells for the use in xenografts; resulting orthotopic cells had vascular hyperplasia, intracranial dissemination and areas of central necrosis.

A 2004 Oncogene article by Zhang et al. used the U118 model in their study of the hepatocyte growth factor (HGF)/scatter factor (SF) interaction with Met in xenografts. Typical xenografts do not replicate HGF/SF-mediated stimulation of the paracrine system, and the results suggested that ectopically expressing human HGF/SF can enhance subcutaneous xenograft growth. The U118 cell line is used to create the CDX (Cell Line Derived Xenograft) U118 xenograft mouse model. The U118 xenograft model has been used to investigate glioblastoma characteristics and therapies.

Basic Study Design

  1. U118 cells are maintained in exponential growth phase under aseptic conditions.
  2. Cells are trypsinized and cell count viability is determined using a trypan blue exclusion assay (98% of cell viability is required).  U118 cell suspension is adjusted to appropriate density.
  3. Each mouse is singly subcutaneously injected into the right flank with 106 cells in 100 µL of a Matrigel- U118 cell suspension.
  4. The injection sites are palpated up to three times weekly until tumors are established to an average size of 50-150 mm3 as measured via digital calipers.
  5. Animals are randomized into treatment groups. Administration of test compound is performed according to the established treatment schedule.
  6. Mice weights are measured and recorded 3 times weekly; tumors are measured and recorded daily.
  7. End of study is reached when tumor size reaches 2,000 mmor the predetermined size limit per approved IACUC protocol.
  8. Final necropsy and tissue collections are performed for appropriate downstream analysis. Tumors are excised, weighed and documented by digital imaging. Tumors and tissues can be stabilized in RNAlater, snap frozen in LN2 or prepared for histology.