Abstract

This review focuses on the properties of different breast cancer cell subsets, including cancer stem cells (CSCs) and cancer progenitors. The premise is that an understanding of self-renewal, the effects of aging microenvironment on the behavior of cancer cell subsets will map the path of development from CSCs to progenitors. The basic characterization of different cancer cell subsets will lead to their signatures and open the field to novel methods of prognosis and diagnosis. The identification of cancer progenitors would allow scientists to modify the cells genetically for dedifferention to CSCs. This will benefit the field to understand the method by which CSCs are developed. The review discusses a reductionist approach for identifying the CSCs and other subsets in bone marrow. An understanding of the mechanisms by which cancer cell subsets interact with other cells of the bone marrow could lead to an understanding of cancer behavior in bone marrow. A protective role of mesenchymal stem cells after the cancer cells enter the marrow is proposed as the first step in the cancer cells forming gap junctional intercellular communication with stromal cells close to the endosteum. It is possible that microRNAs could be shared between the cancer cells and stroma. The review recapitulates two stages of breast cancer: an early stage when the cancer cells enter bone marrow, perhaps prior to clinical detection and during the stage of heavy tumor burden when a subset of cancer cells survive and can resurge years after remission. This review argues for new approaches to identify breast cancer stem cells, and to understand how this population of cells interacts with the bone marrow microenvironment. In summary, the presented approach could lead to the development of new drug targets and approaches to treat breast cancer.

Keywords: Breast cancer, mesenchymal stem cells, gap junction, cancer stem cells, bone marrow