Orthotopic and heterotopic triple negative breast cancer preclinical murine models: A tumor microenvironment comparative

Res Vet Sci. 2022 Dec 20:152:364-371. doi: 10.1016/j.rvsc.2022.08.026. Epub 2022 Aug 31.

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.

Keywords: Air-pouch; Breast cancer; Heterotopic; Mammary fatpad; Orthotopic; Tumor microenvironment.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Models, Animal*
  • Mice
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / veterinary
  • Tumor Microenvironment