Cellular plasticity and metastasis in breast cancer: a pre- and post-malignant problem

Abstract

As a field we have made tremendous strides in treating breast cancer, with a decline in the past 30 years of overall breast cancer mortality. However, this progress is met with little affect once the disease spreads beyond the primary site. With a 5-year survival rate of 22%, 10-year of 13%, for those patients with metastatic breast cancer (mBC), our ability to effectively treat wide spread disease is minimal. A major contributing factor to this ineffectiveness is the complex make-up, or heterogeneity, of the primary site. Within a primary tumor, secreted factors, malignant and pre-malignant epithelial cells, immune cells, stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis. Furthermore, heterogeneity contributes to our lack of understanding regarding the cells’ remarkable ability to undergo epithelial/non-cancer stem cell (CSC) to mesenchymal/CSC (E-M/CSC) plasticity. The enhanced invasion & motility, tumor-initiating potential, and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis. While most work trying to understand E-M/CSC plasticity has been done on malignant cells, recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process. Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor. Moreover, we will discuss how one may potentially target these populations, ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.

Keywords

Cell plasticity / pre-malignant plasticity / breast cancer / epithelial-mesenchymal transition/cancer stem cell / metastasis

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