MDA-MB-157 xenograft model
Metastatic breast cancer is considered the leading cause of death in patients diagnosed with breast cancer. Preclinical xenograft studies can help in discovering innovative treatment options for those affected. Xenograft models mimic the natural environment of cancer development, providing a practical approach to investigate breast tumor pathophysiology and develop novel treatment regimens. The MDA-MB-157 epithelial cell line was derived from the pleural effusion of a 44-year-old female patient with metastatic breast cancer in 1972 by Cailleau at M. D. Anderson Hospital and Tumor Institute, as per a 1980 study in Cancer Research. In addition to being positive for the expression of the WNT7B oncogene, the MDA-MB-157 cell line possesses desmosomes, microvilli and tonofilaments at boundaries between cells. This model has helped further breast cancer research such as in the 2014 Breast Cancer Research article (Zhang et al.) which used MDA-MB-157 xenograft mouse models to study mTOR inhibitors, gene expression and protein levels in triple negative breast cancers (TNBC) which are notoriously aggressive and difficult to treat; they verified that the histologic and genomic profiles of the xenografts matched their original patient tumors and that mTOR inhibitors are effective in slowing growth of TNBC but will need combination therapy to be an effective therapeutic regimen. Another Breast Cancer Research study by Tate et al. (2012) used MDA-MB-157 xenografts as a TNBC model to study a histone deacetylase inhibitor (panobinostat, LBH589) and its ability to selectively target TNBC. Their results showed panobinostat treatment decreased proliferation and survival, halted cell cycle progression, initiated partial mesenchymal-to-epithelial transition and increased histone acetylation in vitro and inhibited tumor formation in vivo, suggesting the TNBC therapeutic potential of panobinostat. Finally, Zheng et al. (2015) used MDA-MB-157 to study a technique to circumvent the protective roles of hypoxia and mitophagy against radiotherapy in aggressive tumors. Their results showed an accumulation of TAT-ODD-p53, a fusion p53 protein that inhibited Parkin-mediated mitophagy and increased sensitivity of tumors to radiotherapy in vivo and in vitro.
The MDA-MB-157 cell line is used to create the CDX (Cell Line Derived Xenograft) MDA-MB-157 xenograft mouse model. The MDA-MB-157 xenograft model is triple-negative (lacking estrogen, progesterone and HER2/NEU receptors) and can be targeted by mono- or combination therapies (e.g. paclitaxel, pretubulin inhibitor, panobinostat).
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Basic study design
- MDA-MB-157 cells are trypsinized and cell viability determined. Trypan blue assay results must exhibit at least 98% cell viability.
- After adjusting cell suspension concentration to one million cells per 100 µL (Matrigel + MDA-MB-157), 10 to 12 week old athymic BALB/C or NOD/SCID mice receive a single subcutaneous injection. All injections are in the rear hind leg flank.
- All injection sites are observed and palpated three times a week until it is determined tumors are established. Tumors are then continually measured (with digital calipers) until an average size of 50-150 mm3is reached.
- Animal randomization into client determined treatment cohorts and administration of compound of interest is performed.
- Daily tumor measurement and mouse weights (3 times weekly) are recorded. Animals are euthanized at the predetermined size limit.
- Tissue collections are performed and can be snap frozen in LN2 and prepared for histological analysis.
- Tumors are weighed and documented (digital imaging).
Altogen Labs provides an array of laboratory services using over 30 standard Cell Line Derived Xenograft (CDX) models and over 20 PDX models. Researchers investigating the role of specific proteins or gene products in regulating tumor growth can benefit from development of protein overexpression (genetically engineered to ectopically express proteins, tumor suppressors, or oncogenes) and RNAi cell lines with long term gene silencing. Altogen Labs provides quantitative gene expression analysis of mRNA expression (RT-PCR) and protein expression analysis using the WES system (ProteinSimple).
Xenograft animal models are used to assess the effectiveness of drugs against specific types of cancer. New medicines are tested on staged tumor growths that have been engrafted via subcutaneous or orthotopic inoculation in an immunocompromised mouse or rat model. All clinically approved anti-cancer agents have been evaluated with conventional preclinical in vivo models. Xenograft studies can be highly complex, starting with the selection of the appropriate animal model, choice of tumorigenic cell line, administration method, dosing, analysis of tumor growth rates and tumor analysis (histology, mRNA and protein expression levels).
The dosing of the experimental compound of interest is initiated, for a staged study, when the mean tumor size reaches a specified volume (typically 50-100 mm3). In an unstaged study, the dosing of the compound of interest is initiated immediately after xenografting. Mice are dosed once or twice a day for 28 days (or other desired study duration) via the chosen route of administration. Tumor volume (mm3) is calculated via the “(W x W x L) / 2” formula, where W is tumor width and L is tumor length.
Animal handling and maintenance at the Altogen Labs facility is IACUC-regulated and GLP-compliant. Following acclimatization to the vivarium environment, mice are sorted according to body mass. The animals are examined daily for tumor appearance and clinical signs. We provide detailed experimental procedures, health reports and data (all-inclusive report is provided to the client that includes methods, results, discussion and raw data along with statistical analysis). Additional services available include collection of tissue, histology, isolation of total protein or RNA and analysis of gene expression. Our animal facilities have the flexibility to use specialized food or water systems for inducible gene expression systems.
Following options are available for the MDA-MB-157 xenograft model:
- MDA-MB-157 Tumor Growth Delay (TGD; latency)
- MDA-MB-157 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)
- MDA-MB-157 tumor immunohistochemistry
- Alternative cell engraftment sites (orthotopic transplantation, tail vein injection and left ventricular injection for metastasis studies, injection into the mammary fat pad, intraperitoneal injection)
- Blood chemistry analysis
- Toxicity and survival (optional: performing a broad health observation program)
- Gross necropsies and histopathology
- Positive control group employing cyclophosphamide, at a dosage of 50 mg/kg administered by intramuscular injection to the control group daily for the study duration
- Lipid distribution and metabolic assays
- Imaging studies: Fluorescence-based whole body imaging, MRI