Kidney Cancer Xenograft

Altogen Labs validated Gastric Cancer Xenograft animal models:

786-O,  A498,  Caki-1,  HEK-293,  Renca,  RXF393,  G401

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.

Kidney cancer, or renal cancer, often develops in the renal pelvis and have many different subtypes that greatly affect prognosis. Kidney cancer detection can be difficult as they are located deep in the body and often do not show symptoms. Possible symptoms include hematuria, one-sided lower back pain, loss of appetite, fatigue, anemia, weight loss and persistent fever. Renal cancer can be detected with a urinalysis or a CT or MRI scan, and are usually found accidentally during treatment of other diseases. Still, kidney cancers are often found at an early stage before metastasis. Types include renal cell carcinoma (RCC, subtypes include clear cell, papillary, chromophome or several rarer types) and transitional cell carcinoma (TCC). RCC is the most common type of kidney cancer and often occur as a single tumor within one kidney. TCC start in the lining of the renal pelvis and the cancer cells are a similar phenotype as bladder cancer. The most common treatment is resection, either partial or complete removal of the kidney, as renal cancer often does not respond well to chemotherapy or radiotherapy. Immunotherapy, primarily interferon and interleukin02, exhibits low (10-15%) success rates; other drug options include nuvolumab, cabozantinib, levatinib, nexavar, axitinib or everolimus. The causes and pathophysiology of renal cancer is not well characterized. Risk factors include obesity, genetics, family history, consistent dialysis, hepatitis C and a history of cancer.

Using human xenograft models of renal cancer, as previously mentioned, is a powerful research tool, and there are many models of kidney cancer to choose from. There are links above to some of the most common tissue culture models that Altogen Labs has available, summarized in the table below. Models are often selected based on morphology, genetics, histology, early vs. late stage phenotype, invasive/aggressive properties, and abnormal protein expressions (usually relating to cell cycle, apoptosis, growth and angiogenesis). The goal of xenografts and murine models is to mirror human pathology and disease as closely as possible so that accurate insights into cellular events are achieved. This aspect is particularly critical with preclinical drug testing for accurately evaluating compound efficacy.

Cell Line Characteristics
786-O ·    Adherent epithelial renal cell carcinoma taken from a primary clear cella denocarcinoma·    Displays microvilli and desmosomes·    Produces PTH-like peptides with similar sequence and activity as PTH

·     Lacks HIF-1α expression and functional VHL; high constitutive HIF-2α expression
A498 ·    Epithelial-like adherent renal cell adenocarcinoma·    Hypertriploid cell line·    Expresses vimentin and cytokeratin 8 and 18; negative in cytokeratin 7, 17, 19, as well as desmin, EpCAM and neurofilament
Caki-1 ·    Epithelial clear cell carcinoma taken from a skin metastatic site·    Aneuploid human cell line with triploid chromosome counts·    Displays microvilli and few filaments

·    Contains many small mitochondria and well-developed Golgi apparatus and endoplasmic reticulum (ER)
HEK-293 ·    Epithelial-like cells derived from human embryonic kidney cells (non-tumor)·    Characteristics of late distal tubules·    Releases urodilatin, the structural analog of ANP

·    Expresses vitronectin receptor

·    Appropriate for transfection and voltage-clamp experimentation
Renca ·    Epithelial Balb/cCr mouse kidney carcinoma·    Mimics human adult renal clear cell carcinoma; exhibits spontaneous metastasis·    Lacks expression of transforming growth factor-beta type II receptor (TbetaR-II)
G401
  • Human epithelial kidney cancer (rhabdoid tumor)
  • Expresses nephroblast growth factor
RXF393 ●        Human renal cell carcinoma

●        Mutated TP53 gene (arg175his)

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 type T cells B cells NK cells Coat Other Notes
CD1 No Yes Yes White/albino Outbred
B6 Yes Yes Yes White/albino Inbred
Balb/c No Yes Yes Nude, albino Inbred
Balb/SCID No No Yes White Inbred
NOD/SCID No No Impaired White Inbred
Nu/nu No Yes Yes Nude Outbred
CD57BL Yes Yes Yes Dark brown/black Inbred
CB17 Yes Yes Yes White Inbred
NSG No No No White Inbred
Swiss Nude No Yes Yes Nude Outbred

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.