Breast Cancer Xenograft

Altogen Labs validated Breast Cancer Xenograft animal models:

4T1 , BT474 , MCF-7 , MDA-MB-231 , MDA-MB-468 , HS578T , MDA-MB-453 , MDA-MB-157 , KPL-4 , T47D, ZR75-1

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.

Breast cancer is the most common malignancy in females. Symptoms often include a lump in the breast, dimpling of the skin and changes in breast shape or nipple behavior. There are many risk factors for developing breast cancer including inherited genetic predispositions such as the well-known BRCA1 and BRCA2 mutations. A tissue biopsy is the used for diagnosis and, as there are over 18 sub-types of breast cancer, gives further information about invasive characteristics and potentially effective treatments. Prognosis varies greatly depending on the cancer subtype and stage, particularly if the breast carcinoma has invaded lymph nodes. Breast cancers can be either ductal or lobular depending on the malignant tissue type and are further classified based on differentiation, staging (i.e. metastatic category), genetics (DNA assays) and receptor status (presence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)). Receptor status is critical for gauging treatment regimens as many chemotherapies, such as tamoxifen and trastuzumab, target these pathways; receptor status can also be a predictor for aggression levels. Common treatment options include radiation (external beam radiotherapy, brachytherapy), chemotherapy (e.g. doxorubicin, docetaxel, fluorouracil, etc.), monoclonal antibody therapy (e.g. trastuzumab), hormone blocking therapy (e.g. tamoxifen, anastrozole, letrazole) or a combination thereof.

Using human xenograft models of breast cancer, as previously mentioned, is a powerful research tool, and there are many models of breast 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, 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
4T1	· Epithelial BALB/cfC3H murine mammary gland tumor· Resistant to 6-thioguanine· Demonstrates spontaneous metastasis with similar kinetics to human cancer · Used to test late-stage therapeutic agents for breast cancer treatment
BT474	· Epithelial human invasive breast ductal carcinoma· Oestrogen receptor and HER2 receptor positive· Poorly differentiated adenocarcinoma with a high proliferative and turnover rate
MCF7	· Epithelial human adenocarcinoma· Expresses progesterone, estrogen and glucocorticoid receptors· Displays differentiated mammary epithelial cell characteristics such as dome formation in culture and ability to process estradiol through cytoplasmic estrogen receptors
MDA-MB-231	· Epithelial metastatic mammary adenocarcinoma· Extremely aggressive triple negative breast cancer (TNBC)· Spindle-shaped cells · CK18 and EGFR positive · Tumor growth is inhibited by Herceptin, lapatinib and trastuzumab
MDA-MB-468	· Derived from a pleural effusion of a human breast adenocarcinoma· Triple negative and often used for metastasis studies and tumor growth inhibitors· Homozygous for a mutated p53 allele
Hs578T	· Epithelial human breast carcinoma· Triple negative breast cancer· Used in studies invasion and the targeting the control of aneuploidy
MDA-MB-453	· Isolated from the pleural effusion of a human epithelial metastatic breast carcinoma· Not tumorigenic· Overexpresses fibroblast growth factor (FGF), androgen receptor (AR) and glycerol 3-phosphate shuttle · ER negative and PR negative but HER2+
MDA-MB-157	· Isolated from the pleural effusion of an epithelial human metastatic breast cancer· Expresses WNT7B oncogene· Possesses microvilli, desmosomes and tonofilaments and cell boundaries · Triple negative breast cancer
KPL-4	· Derived from a malignant pleural effusion from a patient with skin metastasis· Readily metastasizes into lymph nodes· Expresses Erb-B family receptors
T-47D	· Epithelial human ductal breast carcinoma· Estrogen receptor (ER) positive· Hypotriploid karyotype

ZR-75-1

Human epithelial ductal carcinoma derived from metastatic ascitesHypertriploid karyotype

Estrogen receptor positive

Expresses apomucin, MUC-1, MUC-2 but not MUC-3

HCC 1806

Human grade IIB acantholytic squamous cell breast primary carcinoma

Negative for estrogen and progesterone receptors

Expresses EGP2 and cytokeratin 19

Poorly differentiated

HCC1954

Human grade IIA ductal breast carcinoma

Large epithelial cell morphology with occasional vacuoles

Expresses her2/neu (overexpressed), EGP2 and cytokeratin 19

Progesterone and estrogen receptors not expressed

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

The breast cancer xenograft models allows for the study of tumor growth and response to test article treatment. The process of breast cancer tissue xenotransplantation involves implanting a small piece of breast tumor tissue from a human patient into an animal, often into the mammary fat pad (orthotopic) or under the skin (subcutaneous). The tumor is allowed to grow and develop in the animal host, and its growth is monitored and studied over time. Breast cancer xenograft models are used to study the biology of breast cancer, including the mechanisms of tumor growth and metastasis, as well as the tumor’s response to various treatments types. There are many different types of breast cancer, and different subtypes may behave differently in xenograft models. For example, estrogen receptor-positive (ER+) breast cancers, which account for about 70% of all breast cancers, represent different tumor growth characteristics compared to xenograft models with estrogen receptor-negative (ER-) breast cancers.

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.

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 2^nd 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.