Related Experiment Video
Updated: Aug 28, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Orthotopic and heterotopic triple negative breast cancer preclinical murine models: A tumor microenvironment
Silvia Elena Santana-Krímskaya1, Jorge R Kawas2, Diana Ginette Zarate-Triviño1
1Universidad Autónoma de Nuevo León (UANL), Facultad de Ciencias Biológicas, Laboratorio de Inmunología y Virología, C.P. 66455, Pedro de Alba s/n, Ciudad Universitaria, San Nicolás de los Garza, NL, Mexico.
Abstract:
Breast cancer is the most frequent type of cancer worldwide and triple negative breast cancer is a particularly aggressive subtype. Novel therapies for the treatment of cancer patients focus on the remodeling of the tumor microenvironment (TME). Orthotopic and heterotopic syngeneic mice are the most common model used to study the TME in preclinical research. Despite this, there are no published studies that address the differences between orthotopic and heterotopic murine breast cancer models at the TME level. In this report we compared proliferation, immune cell infiltrates, extracellular matrix, vascular density, and response to chemotherapy between the mammary fat pad orthotopic model, and the air pouch heterotopic model. Our study shows that the orthotopic tumors form more metastasis, however, the heterotopic tumors grow larger, have a higher FOXP3 cell infiltrate, and resemble more accurately the breast cancer TME. Our findings show that both models are very similar, there are however some differences that should be considered in the experimental design of preclinical studies.
Insights
Comparing breast cancer models in mice, this study found that while orthotopic models show more metastasis, heterotopic models better mimic the tumor microenvironment (TME). These findings aid preclinical research design for novel cancer therapies.
Area of Science:
- Oncology
- Cancer Research
- Preclinical Models
Background:
- Breast cancer is a global health concern, with triple-negative breast cancer being highly aggressive.
- Novel cancer therapies aim to remodel the tumor microenvironment (TME).
- Orthotopic and heterotopic syngeneic mouse models are crucial for studying the TME in preclinical research.
Purpose of the Study:
- To compare orthotopic and heterotopic murine breast cancer models at the TME level.
- To evaluate differences in proliferation, immune cell infiltration, extracellular matrix, vascular density, and chemotherapy response.
- To inform the experimental design of preclinical breast cancer studies.
Main Methods:
- Comparison of mammary fat pad orthotopic and air pouch heterotopic syngeneic mouse models.
- Assessment of tumor metastasis, growth, immune cell infiltrates (including FOXP3+ cells), extracellular matrix, and vascularization.
- Evaluation of response to chemotherapy.
Main Results:
- Orthotopic tumors exhibited increased metastasis.
- Heterotopic tumors demonstrated larger growth and higher FOXP3 cell infiltration.
- Heterotopic models more accurately recapitulated the breast cancer TME compared to orthotopic models.
- Both models showed similarities, but key differences were identified.
Conclusions:
- Orthotopic and heterotopic mouse models for breast cancer present distinct characteristics relevant to TME research.
- Heterotopic models may offer a more accurate representation of the breast cancer TME, particularly regarding immune cell infiltration.
- Understanding these differences is critical for optimizing preclinical study designs and translational success in breast cancer therapy development.
