Animal models serve as a vital bridge between in vitro cell-based assays and human clinical trials, allowing for the study of tumor initiation, progression, metastasis, and response to therapy within a complex biological system. Protheragen's prostate cancer animal model development services integrate cutting-edge gene-editing technologies, multi-omics analysis, and high-resolution imaging to bridge preclinical discovery and clinical application.
Introduction to Prostate Cancer Animal Models
Prostate cancer (PC) remains one of the most prevalent malignancies among men globally, with metastatic castration-resistant prostate cancer (mCRPC) accounting for the majority of mortality. Animal models are indispensable for elucidating tumor biology, metastasis mechanisms, and therapeutic responses. Ideal models must replicate human prostate cancer's heterogeneity, including androgen dependency, neuroendocrine differentiation, and bone-tropic metastasis. Traditional models, such as chemically induced or spontaneous tumors, have limitations in translational relevance, prompting the development of genetically engineered, patient-derived xenograft (PDX) and syngeneic systems.
Fig.1 Widely used methods for generation of transgenic mice. (Onaciu A.,
et al., 2020)
Types of Prostate Cancer Animal Models
- Patient-Derived Xenograft (PDX) Models
Considered the gold standard for many preclinical studies, PDX models are created by directly implanting human tumor tissue from a patient into an immunocompromised mouse. This approach preserves the tumor's genetic heterogeneity, histological architecture, and stromal elements, providing a highly predictive platform for personalized medicine and late-stage drug testing. PDX models are particularly valuable for studying castration-resistant PCa (CRPC) and for identifying effective therapies for individual patients, a cornerstone of Protheragen's precision medicine offerings.
- Cell-Line Derived Xenograft (CDX) Models
These traditional models involve the subcutaneous or orthotopic implantation of established human PCa cell lines (e.g., LNCaP, PC-3, DU145) into immunocompromised mice. While they may not fully capture the genetic diversity of patient tumors, CDX models offer a highly reproducible and cost-effective platform for initial compound screening and efficacy studies. Their predictable growth kinetics make them an excellent tool for pharmacokinetics and pharmacodynamics (PK/PD) studies.
- Genetically Engineered Mouse (GEM) Models
GEM models are created by introducing or inactivating specific genes in the mouse genome to drive tumor formation. Models like the TRAMP (Transgenic Adenocarcinoma of the Mouse Prostate) model, which expresses the SV40 T-antigen, spontaneously develop prostatic tumors. Newer GEM models utilize Cre-LoxP systems to conditionally delete key tumor suppressor genes (e.g., Pten, p53) in a prostate-specific manner. These models are invaluable for studying the mechanisms of cancer initiation and progression, allowing for a deeper understanding of the molecular drivers of the disease.
- Syngeneic Models
For immunotherapeutic approaches, syngeneic models are essential. These models involve the transplantation of mouse tumor cell lines into immunocompetent, genetically identical mouse strains. This ensures that the tumor grows within a functional host immune system, allowing researchers to accurately evaluate the anti-tumor effects of immunotherapies, such as checkpoint inhibitors and vaccines. The absence of a foreign immune response provides a crucial context that is absent in xenograft models.
Our Services
At Protheragen, we offer an end-to-end suite of services designed to accelerate your preclinical research. Our deep scientific expertise and state-of-the-art facilities ensure the highest quality and reliability in every study.
Protheragen employs well-established chemical induction methods to generate reliable prostate cancer models in rodents, facilitating the study of tumorigenesis and the efficacy of novel treatments. Our expertise covers:
N-methyl-N-nitrosourea (MNU) Model
This model utilizes MNU, a genotoxic agent that directly interacts with DNA to induce mutations. Administered typically via injection to rats, MNU can effectively and relatively rapidly induce prostate cancer. While this model can lead to multifocal tumors and may affect multiple organs, it provides a valuable tool for studying early-stage carcinogenesis and screening interventions.
3,2'-Dimethyl-4-aminobiphenyl (DMAB) Model
DMAB is a polycyclic aromatic hydrocarbon that forms DNA adducts, leading to DNA damage and mutations. Administered orally or by injection to mice, this model is generally straightforward to manage and control. It is particularly useful for studying mechanisms related to environmental carcinogens and their role in prostate cancer development, though potential differences in metabolic pathways compared to humans warrant careful consideration.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Model
PhIP, a heterocyclic amine formed during the cooking of meats, is metabolized in vivo to reactive intermediates that can damage DNA. By incorporating PhIP into the diet of mice, we can simulate aspects of human dietary exposure and induce prostate cancer. This model is instrumental in exploring the link between environmental factors, diet, and prostate cancer. It allows for the investigation of specific metabolic pathways and mechanisms of PhIP-induced carcinogenesis.
Syngeneic models, utilizing well-characterized prostate cancer cell lines within animals of the same genetic background, are invaluable for studying tumor-host interactions, immunotherapy, and drug efficacy. Protheragen provides access to key syngeneic models:
- RM1 Model: Derived from a prostate cancer cell line in C57BL/6 mice, the RM1 model is perfectly matched to the C57BL/6 genetic background. This allows for the successful establishment of syngeneic tumors via both subcutaneous and orthotopic implantation. This model is frequently used for evaluating therapeutic responses and understanding tumor microenvironment dynamics.
- MyC-CaP Model: Originating from prostate tumor cells of the TRAMP transgenic mouse model, the MyC-CaP cell line can be transplanted into male FVB/N mice of the same genetic background to create syngeneic tumors. Notably, MyC-CaP cells express androgen receptors and are androgen-sensitive, making this model highly relevant for studying therapies targeting the androgen axis in prostate cancer.
Protheragen provides access to a broad panel of well-characterized human prostate cancer cell lines for CDX model development, including but not limited to:
| Model Types |
Conditional Knockout Mice |
Point Mutation Knockin Mice |
| Model Name |
Braf-Flox Mice |
Braf-Flox-V600E Mice |
| Also Known As |
C57BL/6-Brafem1(flox) |
C57BL/6-Brafem1(flox-V600E) |
| Detailed Description |
These mice harbor loxP sites flanking Exon 5 of the Braf gene. When crossed with a Cre recombinase-expressing strain, they enable tissue-specific conditional knockout of the Braf gene. |
These mice harbor a conditional p.V600E mutation in the Braf gene. |
| NCBI ID |
109880 |
109880 |
| MGI ID |
88190 |
88190 |
| Gene Alias |
B-raf, Braf2, Braf-2, C87398, AA120551, AA387315, AA473386, C230098H17, D6Ertd631e, 9930012E13Rik |
B-raf, Braf2, Braf-2, C87398, AA120551, AA387315, AA473386, C230098H17, D6Ertd631e, 9930012E13Rik |
| Chromosomes |
Chr 6 |
Chr 6 |
| Sales Status |
Embryo cryopreservation |
Repository live |
| Applications & Therapeutic Areas |
Study on the correlation between meiosis and RET signal transduction in oocytes
Melanoma; Thyroid Gland Papillary Carcinoma; Skin Melanoma; Prostate Cancer; Langerhans-Cell Histiocytosis; Cardiofaciocutaneous Syndrome |
Cancer research
Melanoma; Thyroid Gland Papillary Carcinoma; Skin Melanoma; Prostate Cancer; Langerhans-Cell Histiocytosis; Cardiofaciocutaneous Syndrome |
| Ensembl ID |
ENSMUSG00000002413 |
ENSMUSG00000002413 |
| Pubmed |
Braf |
Braf |
| Human Ortholog |
BRAF |
BRAF |
Case Study
Protheragen has successfully developed a subcutaneous prostate cancer xenograft animal model using CB17 SCID mice and the 22 Rv1 cell line for the study of prostate cancer. This model has been validated by monitoring tumor growth and body weight changes in the mice, which have demonstrated the successful establishment of the prostate cancer model. This model provides a valuable tool for researchers to study the progression of prostate cancer and to test the efficacy of potential therapeutic interventions.
Fig.2 Tumor growth and body weight changes in the subcutaneous transplantation model of 22 Rv1 cells.
Prostate cancer animal models are essential tools in advancing our understanding of the disease and developing effective prevention and therapeutic strategies. At Protheragen, we offer a comprehensive suite of services for developing and maintaining these models, ensuring that researchers have access to high-quality, relevant tools for their studies. If you are interested in our services, please feel free to contact us.
References
- Onaciu, Anca, et al. "Spontaneous and induced animal models for cancer research." Diagnostics 10.9 (2020): 660.
- Ittmann, Michael, et al. "Animal models of human prostate cancer: the consensus report of the New York meeting of the Mouse Models of Human Cancers Consortium Prostate Pathology Committee." Cancer research 73.9 (2013): 2718-2736.
- Pienta, Kenneth J., et al. "The current state of preclinical prostate cancer animal models." The Prostate 68.6 (2008): 629-639.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
