Mouse models of breast cancer metastasis

Breast cancer metastatic mouse models are experimental approaches in which mice are genetically manipulated to develop a mammary tumor leading to distant focal lesions of mammary epithelium created by metastasis. Mammary cancers in mice can be caused by genetic mutations that have been identified in human cancer. This means models can be generated based upon molecular lesions consistent with the human disease. Metastasis is a process of migration of tumour cells from the primary cancer site to a distant location where the cancer cells form secondary tumors. Metastatic breast cancer represents the most devastating attribute of cancer and it is considered an advanced-stage event. Human breast cancer metastasizes to multiple distant organs such as the brain, lungs, bones and liver. The classical theory developed in the early 70's anticipated that metastasis is due to genetically determined subpopulations in primary tumours. The genetic variance between metastatic foci is significant for only particular locus and within specific cell populations or only one-cell population shows differences and some loci are divergent only in one cell subpopulation. This explains the concept of tumour heterogeneity and the order of genetic events during tumor evolution. Many of the genes driving the growth at primary site can determine the dissemination and colonization at the ectopic site. Breast cancer is consensually considered genetically and clinically as a heterogeneous disease, in that it reflects the heterogeneity of the normal breast tissue at its origin17873350. A number of discrete genetic events have to occur in order to enable individual tumor cells that have the capacity to grow at an ectopic site. The metastatic progression depends on the regulation of developmental programs and environmental events. The metastatic potential of sub populations within mouse mammary cells is now considered as relatively an early event and dissemination occurs at the same time of pre invasive or micro-invasive lesions.