Melanoma Xenograft

Altogen Labs validated Melanoma Xenograft animal models:

A2058,  A375,  B16,  SK-MEL,  A431

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.

Melanoma, or malignant melanoma, is a cancer that develops from melanocytes, which produce pigment in the skin (but can rarely occur in the eye, intestines or mouth). Symptoms of melanoma include a mole that increases in size, has irregular edges, changes in color, or itchiness and skin breakdown. The sun and tanning devices (ultraviolent light exposure) is known to cause melanoma and risk factors include family history, a large number of moles and poor immune function. Diagnosis is typically done via initial visual identification with a dermatoscope followed by tissue biopsy to confirm. Lactate dehydrogenase tests are often done to screen for metastasis, and the presence of S-100 and HBM-45 are also signs of primary melanoma or metastasis. Types of melanomas include lentigo maligna, lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma, mucosal melanoma, nodular melanoma, polypoid melanoma and desmoplastic melanoma among others. Treatment is often limited by surgery (excisional biopsies) and as melanomas typically spread to lymph nodes before other sides a lymphadenectomy or fine-needle aspiration may also be performed. Lymphoscintigraphy can be performed to localize sentinel nodes. For more advanced cases of melanoma, isolated limb infusion (ILI) of chemotherapy has been found to be successful for treating regional melanomas. Targeted therapies (BRAF, C-Kit and MEF inhibitors such as trametinib, vemurafenib, dabrafenib), immunotherapies (against cytokines, or anti-CTLA-4 monoclonal antibodies such as ipilimumab and tremelimumab, TLR agonists, PD-1 antibodies, CD40 agonists, etc.) and radiotherapies are also used. Localized melanomas have a nearly 100% 5-year survival rate and are typically caught at an early enough stage however once regional or distant advanced melanomas develop (especially with lymph node metastasis) prognosis is much poorer. The presence of tumor-infiltrating lymphocytes is a marker that improves prognosis.

Using human xenograft models of lymphoma, as previously mentioned, is a powerful research tool, and there are several models of lymphoma 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
A2058 ·    Human malignant melanoma line from a lymph node metastasis

·    Expresses nerve growth factor (NGF) and laminin

·    Used for elevated pERK and pAKT studies

A375 ·    Epithelial human malignant melanoma

·    Used for studying skin infections, and BRAF and BCL-2 inhibitors

·    Hypotriploid karyotype

B16 ·    Murine melanoma cell line (C57BL/6)

·    Used to screen anti-proliferation therapies such as simvastin and paclitaxel

·    Epithelial-like and spindle shaped cells

MEL-2 ·    Human epithelial cells from the thigh of of a malignant melanoma patient

·    Expresses wild-type B-Raf and mutant N-Ras

·    Polygonal morphology

A431 ·    Epithelial human cell line from an epidermoid carcinoma patient

·    Overexpresses EGFR

·    No functional p53

·    Hypertriploid karyotype

 

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.