The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the "Seed" and the "Soil"?

Abstract

Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs), has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly ineffective against metastatic breast cancer, likely due to the innate therapy resistance of CSCs and the complex interactions that occur between cancer cells and their metastatic microenvironments. A better understanding of these interactions is essential for the development of novel therapeutic targets for metastatic disease. This paper summarizes the characteristics of breast CSCs and their potential metastatic microenvironments. Furthermore, it raises the question of the existence of a CSC niche and highlights areas for future investigation.

Figure 1

Potential factors involved in the organ-specific metastasis of breast cancer to the brain, liver, lymph nodes, lung, and bone. Brain, lung, and liver images were acquired with thanks to Creative Commons Licensing (CC0 1.0, Public Domain Dedication). Bone image from Gray's Anatomy (1918, Public Domain, copyright expired). Underlining indicates tumor-derived factors. Italics indicate organ-derived factors. *indicates factor identified by microarray analysis of organ-specific metastatic cell line variants [–59].