Breast cancers, mammary stem cells, and cancer stem cells, characteristics, and hypotheses

Abstract

Highlights Breast cancer is a complex disease arising from the association and cumulation of multiple genetic alterations and environmental factors likely to alter cellular functions. The implication of stem cells in breast cancer’s origin and development has been debated for many years. Analogies between stem cells and cancer cells can be drawn on many levels. Importantly not all cancer cells are stem cells or exhibit properties similar to stem cells. There is no universal cell surface marker of the breast cancer stem cells, imputable to the diversity of the cell of origin, the heterogeneity and fluidity of the microenvironments, and a plethora of possible mutational events. Breast cancer stem cell targeting should hold a great promise for preventing metastasis, reducing the risk of drug resistance, and decreasing recurrence. However, only a few clinical trials assess the effectiveness of treatments on this specific cancer cell population. Additional considerations for the targeting of breast cancer stem cells need to be given to the tumor microenvironment. It is known to promote self-renewal, plasticity, and resistance to treatments. The fate of breast cancer stem cells is indissociable from its environment.

LncRNAs and microRNAs as Essential Regulators of Stemness in Breast Cancer Stem Cells

“…Several cell surface markers have been used for the identification of MaSCs in human and mice mammary tissues. This includes epithelial cell adhesion molecule (EpCAM), Procr, sca-1, Myh11, CD61, CD133, CD10, CD24, CD29, CD49f, CD49b, c-Kit, THY1, Lrp5, Axin2, CK5, CK8, CK14, CK18, CK19, Lgr5, Lgr6, and CD1d [ 14 ]. The mammary gland tissue has a high regeneration capacity, high proliferative capability, and plasticity due to its capacity to generate the whole organization’s epithelial and cell complex hierarchy, whose organization and functioning depends on diverse signaling pathways that maintain cellular homeostasis [ 15 ].…”

“…BC is characterized by a high degree of intratumoral heterogeneity, so its classification varies between patients, which exerts a direct effect on the selection of treatment, so this heterogeneity determines tumor evolution [ 14 ]. The precise origin of bCSCs is ambiguous and has been controversially debated for a long time.…”

“…Several similar features exist between cancer cells and bCSCs. Both types of cell can self-renew and share signaling pathways associated with cell replication and maintenance [ 14 ]. Particularly, two nonexclusive BC models have been proposed to explain the presence of clonal populations in tumors.…”

“…The accumulation of genetic and epigenetic alterations results in the development of at least one cell with CSC traits that can produce more CSCs and more differentiated offspring. In the past, the CSC model was thought to be a static one; in recent times, it has been revised to a dynamic one, where CSCs are believed to convert into more transient cell types [ 14 , 36 ]. It is important to mention the heterogeneity of cancer cells; not all cancer cells are stem cells or exhibit properties similar to stem cells.…”

“…The hierarchical or CSC model postulates that only a small proportion of tumor cells residing in the tumor have tumor-propagating potential. These cells exhibit self-renewal properties and are capable of reiterating tumor hierarchy [ 14 , 36 , 37 ]. The bCSCs are on top of a hierarchy of cells that form the tumor.…”