Orthotopic tumor inoculation allows organotypical interactions between cancer cells and surrounding environment thereby permitting the expression of the biological tumor nature in terms of growth rate, morphology and differentiation, metastasis, and tumor cell sensitivity to therapies.
Based on surgical breast tumor cell inoculation into the fourth mammary fat pad of immunocompetent mice, our syngeneic orthotopic 4T1 breast tumor-bearing mouse model, which is an aggressive model of human breast carcinoma, has indeed many characteristics that make it a suitable experimental tool for human breast cancer. In addition to their poor immunogenicity – a characteristic shared with human mammary cancers, 4T1 tumor cells are easily implanted into the mammary fat pad thereby allowing for the growth of the primary tumor in the anatomically correct site. Moreover, 4T1 model is capable of spontaneous metastasis to several organs including and not limited to lungs and liver, in a pattern that is analogous to human mammary cancer. Metastases begin while the primary tumor is in place but are heterogenous and not detectable in all animals.
In an interesting way, the model is characterized by the presence of at least two types of tumor-infiltrating immunosuppressive cells – myeloid suppressive cells (MSC) and T regulatory cells (Treg). Such cell populations are known, as a result, to suppress T cell responses and thus promote tumor immune escape and metastasis.