Brain Cancer Xenograft

Altogen Labs validated Brain Cancer Xenograft animal models:

U87 MG,  LN229U87-LucSK-N-ASSF268SF295,  SF539SNB75,  SNB19,  UG-251MG

Xenotransplantation studies have been a backbone of oncology research for four decades, and provide an effective research and evaluation environment for novel pharmaceutical compounds. Typically, these studies involve the implantation of tumorigenic human cell lines into immunocompromised mice, providing scientists with an in vivo model of tumor behavior in which to perform experiments including screening of novel cancer therapies, studies of cell behavior, and examination of metastasis. Patient-derived xenografts are a fundamental part of in vivo pharmacological research, aiding in the translation from benchtop to bedside.

Malignant brain tumors can be primary tumors that originated in the brain or secondary that are a result of metastatic spread from other organs. Symptoms of brain tumors often include seizures, vision problems, vomiting, headaches and mental changes. There are several main types of primary brain tumors that are typically categorized by the cell type from which they originate. Gliomas are the most common type of malignant primary brain cancer and originate from glial cells. Glioblastoma multiforme (GBM) is the most aggressive cancer; it is a grade IV glioma and prognosis is typically 12-17 months. Astrocytomas are the malignant form of astrocytes which are star-shaped glial cells found in the cerebrum. Medulloblastoma is a pediatric primary glioma that grows rapidly and can spread through cerebrospinal fluid and forms from malignant neurons. Meningioma is cancerous meninges, which are three membranes that protect and cover the brain and spinal cord. Meningiomas are often slow-growing and have a recurrence rate of <20%. Other types include ependymoma, adenoma and oligodendroglioma.

Using human xenograft models of gliomas, as previously mentioned, is a powerful research tool, and there are many models of brain cancer to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, also detailed in the table below. Models are often selected based on morphology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). Also used are luciferase-expressing models (ex. U87-LUC), which are useful for bioluminescent imaging of the xenografted tumors.

Cell LineCharacteristics
U87 MG·    Epithelial-like glioblastoma derived from a stage 3 patient

·    Distinct from parent line U87

·    Often used to study siramesine, a lysosomal destabilizing drug, and the effects of nanosecond pulsed electric fields on calcium-independent disruption on microtubule dynamics

·    Also available as a luciferase expressing line

LN229·    Epithelial glioblastoma isolated from a patient with frontal parieto-occipital glioblastoma

·    Often used in apoptosis studies (i.e. Fas ligand and puromycin treatment)

·    Wild type PTEN, mutant p53 and potential homozygous deletions in the genes for p16 and p14ARF (tumor suppressors)

SK-N-AS·    Human neuroblastoma derived from a bone marrow metastasis

·    Poorly differentiated polygonal nerve cell type

·    Expresses vimentin

·    Hyperdiploid karyotype

·    Overexpresses IGF-2 leading to autonomous replication

·    Overexpresses PLK-1, used in PLK-1 inhibitor studies (e.g. BI 2536)

·    Used for neuroblastoma differentiation studies

SF268·    Human astrocytoma of the right parietal lobe

·    Highly anaplastic without distinct morphology, highly proliferative, aggressive

·    High gene expressions of EEF1A1, TMSB4X, TMSL3, RPS17, RPL41,  RPL23A, ACTB, RPL37A, ACTG1, RPS25

SF295·    Undifferentiated human glioblastoma

·    Homozygous for genes PTEN and TP53

·    Late stage phenotype

SF539·    Isolated from a recurrent glioblastoma of the right temporoparietal lobe after treatment

·    Expresses collagen type IV, procollagen type III, laminin and fibronectin

·    Used in testing combination therapies

SNB19·    Isolated from a glioblastoma of the patient’s left parieto-occipital lobe

·    Secretes plasminogen activator, uPAR and cysteine protease cathepsin B

·    High-grade glioma

UG-251MG·    Isolated from human malignant glioblastoma astrocytoma

·    Highly invasive pleomorphic astrocytoids with GFAP positive cells

·    Expresses PDGFR and EGFR receptors

·    Contains mu-p53 and mu-PTEN

SNB75·    Derived from a human grade IV glioblastoma (non-epithelial)

·    Homozygous for TP53

·    Widely used for drug screening

Altogen Labs is one of the leading biology contract research organization (CRO) based in Austin, Texas. Altogen Labs provides years of expert research in xenograft experiments taking advantage of the comprehensive expertise the company has developed in the use of human tumor xenografts for research and clinical purposes. Altogen Labs offers a complete suite of laboratory services, including:

  • xenotransplantation study design
  • selection of appropriate cancer model/cell line
  • host animal selection
  • subcutaneous or orthotopic xenografting
  • daily observation of experimental subjects
  • post-experiment analysis, including serum collection and histology

Mouse strains available at Altogen Labs:

Mouse typeT cellsB cellsNK cellsCoatOther Notes
CD1NoYesYesWhite/albinoOutbred
B6YesYesYesWhite/albinoInbred
Balb/cNoYesYesNude, albinoInbred
Balb/SCIDNoNoYesWhiteInbred
NOD/SCIDNoNoImpairedWhiteInbred
Nu/nuNoYesYesNudeOutbred
CD57BLYesYesYesDark brown/blackInbred
CB17YesYesYesWhiteInbred
NSGNoNoNoWhiteInbred
Swiss NudeNoYesYesNudeOutbred

 

About the models

CD1

This model originates from a non-inbred Swiss stock of the 1920s from the Centre Anticancerux Romand (Lausanne, Switzerland). Outbred stocks are generally used for their genetic variability.

B6

This strain of mouse arose from a spontaneous mutation in the C57BL/6 strain resulting in a coisogenic albino mutant. These mice have a mutant tyrosinase gene.

Balb/c

This strain of nude mouse was developed in the 1980s through many crosses and backcrosses and remains to be an inbred model. Balb/c mice do not have a thymus and therefore cannot produce T-cells and are considered immunodeficient. Balb/c mice are often used for their easy breeding and similar weights (low-variation) of males and females. They are also used for monoclonal antibody production.

Balb/SCID

This mouse model lacks functioning T and B cells but do have functioning NK cells which limits engraftment. These mice are sensitive to irradiation and have functioning macrophages, dendritic cells and complement activity. Some cancer cell lines show improved engraftment over nude models in Balb/SCID mice.

NOD/SCID

The homozygous SCID mutation results in impaired T cell and B cell lymphocyte development. The NOD characteristic results in impaired natural killer cell function. NOD/SCID mice also lack macrophage and dendritic cell activity as well as reduced complement activity. These mice have a non-obese diabetic and insulitis background and low cytokine production. NOD/SCID mice exhibit a 36-week median survival due to the development of thymic lymphomas, which limits their use to short-term experiments.

Nu/nu

These mice originate from the National Institute of Health (NIH). Originally thought to be BALB/C congenic mice, once it was discovered that these mice were outbred they were determined to be of their own strain. These mice do not have a thymus, or T-cells, and are nude immunodeficient models.

CD57BL/6

This laboratory mouse strain was the 2nd mammalian species to ever have its genome published in entirety. They originate from the Bussey Institute for Research in Applied Biology in 1921. These mice are often selected for easy breeding and availability of congenic strains. These mice are particularly sensitive to odors, noise, pain, cold, alcohol and morphine addiction.

CB17

CB17 mice are of a congenic strain that carry the immunoglobulin heavy chain allele (Igh-1b) from a C57BL/Ka on a BALB/c background. They are an ideal control for the CB17/SCID immunodeficient mouse model

NSG

Also known as NOD scid gamma, these mice are deficient in NK, T and B cells as well as multiple cytokine pathways. They also have reduced dendritic cell function and defective macrophage activity and lack a complement system. They are one of the most immunodeficient models available and unlike NOD/SCID mice, NSG mice do not develop thymic lymphomas and can be used for long-term experiments.

Swiss Nude

These mice originate from the 1974 Gustave Roussy Institute (Villejuif, France) Swiss stock. They are T cell deficient, nude and albino.

All laboratory studies are performed by experienced personnel in a GLP-compliant and IACUC-regulated facility in Austin, Texas. Please contact us at info@altogenlabs.com, or call 512-433-6177 to discuss xenograft study details.