U87 Xenograft Model

U-87 MG xenograft model

U87 xenograft is a widely used model of human glioblastoma multiforme (GBM), a highly aggressive and malignant form of brain cancer. The U87 xenograft model is created by injecting human U87MG glioblastoma cells into immunodeficient mice, which allows the cancer cells to grow and form tumors that closely resemble human GBMs. Malignant glioblastoma is the most common type of primary brain tumors in adults that is incurable in most cases. According to the American Cancer Society, glioblastoma is one of the deadliest types of cancer that has a median survival time of fewer than 15 months. This form of cancer usually has a high recurrence rate with the 5-year survival rate of nearly 3% to 5% and is very challenging to eradicate. The U-87 MG epithelial cell line was isolated in 1966 at Uppsala University in Sweden from a 44-year-old Caucasian female patient with Stage 3 glioblastoma. It is an extensively studied cell line that has been analyzed in numerous publications for over four decades. In a 2010 study, published in PLOS Genetics, the U-87 MG cell line was evaluated and discovered to have a large number of chromosomal abnormalities. The modal chromosome number of 44 occurs in 48% of cells, only one copy of the normal X chromosome is present and N1, N6 and N9 are absent entirely. Additionally, a homozygous mutation in PTEN was identified. Kiaris et al. (2000) published a study in Clinical Cancer Research using the U-87 line to investigate potential inhibiters of somatostatin (SST) receptors in brain tumors. They identified the compound AN-238, an analogue derivative of doxorubicin, as a treatment that successfully inhibited growth of U-87 glioblastoma in nude mice. A 2008 study by Tseng et al. used a U-87 subcutaneous xenograft model in nude mice to test the preclinical efficacy of using microPET scanning to monitor ¹⁸F-FDG (a proliferation tracer) accumulation in tumors as a method of early therapy monitoring. They found that the c-Met inhibitor CE-355621 treated tumors exhibited lower levels of ¹⁸F-FDG, indicating a successful decrease in tumor growth and supporting the use of this method for human clinical trials.

In xenotransplantation, cancer cells are transplanted into immunodeficient mice to assess the response of cells to novel drugs and research the progress of the disease. The U-87 MG cell line is used to create the CDX (Cell Line Derived Xenograft) U87 xenograft mouse model. The U-87 MG xenograft model contains wild-type p53 status. The U87 xenograft has historical significance as a proven model when assessing glioblastoma angiogenesis and anti-angiogenic therapeutic agents.

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Basic study design

1. Exponential growth of cells is maintained for U87 cells prior to injection.  Trypsin-EDTA is used to collect cells, which is followed by trypan blue (cell viability) cell counting.  The cell concentration is then diluted to 10,000 cells/µL.
2. Twelve (12) weeks old athymic BALB/c nude mice receive an s.c. injection.  All inoculations are made into the hind leg and contain Matrigel plus U-87 MG cells.  Tumor measurements are made using calipers.  Upon averages of 120-150 mm³, the animals are grouped into the number of treatment cohorts needed for the study.  In-life dosing of all test compounds are performed following the client supplied schedule.
3. Continual tumor measurements (e.g. daily) and whole body weights are logged.  At the end of the study, tumors are weighed and then documented (optional digital imaging).
4. In preparation for future downstream analysis, tumors/tissues are stored according to client instructions, including options such as samples being stabilized (RNAlater), snap frozen or prepared for histology (10% NBF).

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U-87 MG Xenograft Model

U87-MG is a human glioblastoma cell line that was derived from a malignant brain tumor in a patient. The cells are widely used in research as a model for studying the biology of glioblastoma and testing potential treatments for the disease. U87MG cells have been extensively characterized and are known to harbor several genetic mutations, including mutations in the tumor suppressor gene p53 and the oncogene EGFR. These mutations are commonly found in glioblastoma tumors and are thought to contribute to tumor growth and resistance to therapy. One of the notable features of U87MG cells is their ability to invade surrounding tissues, a property that is typical of glioblastoma tumors in patients. U87MG cells are also used as a model system for testing potential glioblastoma therapies.

Following options are available for the U87 xenograft model:

• U87 Tumor Growth Delay (TGD; latency)
• U87 Tumor Growth Inhibition (TGI)
• Dosing frequency and duration of dose administration
• Dosing route (intravenous, intratracheal, continuous infusion, intraperitoneal, intratumoral, oral gavage, topical, intramuscular, subcutaneous, intranasal, using cutting-edge micro-injection techniques and pump-controlled IV injection)
• U87 tumor immunohistochemistry
• Alternative cell engraftment sites (orthotopic transplantation)
• Blood chemistry analysis
• Toxicity and survival (optional: performing a broad health observation program)
• Gross necropsies and histopathology
• Positive control group employing cisplatin, dox, or cyclophosphamide
• Imaging studies: Fluorescence-based whole body imaging

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U87 Xenograft Model