What are markers for breast cancer stem cells ?

Breast cancer stem cells were firstly discovered by Al-Hajj et al. (2003). Many scientists interested in targeting them as an important solution to "remove" the root of breast cancer. However, more and more publications showed that breast cancer stem cells are the heterogenous population that expression of some markers can be different between them. Particularly, some different markers were considered as markers of breast cancer stem cells. Therefore, what are gold standards of these cells? In this publication, we discussed some conflicts about markers of breast cancer stem cells and suggested some gold standards for breast cancer stem cells.

In a study involving 61 patients with breast cancer, normal breast tissue and breast tumor tissue from the same patients were analyzed to determine the presence of stem cells in both the tissues.In all, nine patients had triple-negative cancer (TNC) and 52 patients had ER + and Her2 + cancer.The results showed that 100% (9/9) patients with TNC had CSCs with CD44 + CD49f + CD133/2 + phenotypein both the normal and tumor tissues and that only 13.4% (7/52) patients with ER + and/or Her2 + cancerhad CSCs in the normal breast tissue.
Based on this result, Atkinson et al. (2013) proposed that CSCs in breast cancer originated from mutated mammary stem cells present in the normal breast tissue (Atkinson, et al., 2013).
The idea that breast CSCs were derived from non-stem cells originated from the heterogeneity of breast cancer cell lines.Almost all breast cancer cell lines contain a subpopulation of cells with breast CSC phenotypes.Interestingly, some studies have shown that different subpopulations of cells in the same breast cancer cell line can interconvert between phenotypes.

Some recent studies have shown that actively transdifferentiated breast non-CSCs can be converted into
CSCs after treatment with some defined factors.CSC-like cells were produced after the transfection of MCF10Acells with SRC oncogene (Iliopoulos, et al., 2011).Moreover, the CSC-conditioned medium can convert non-CSCs into CSCs (Iliopoulos, Hirsch, Wang and Struhl, 2011).Shaffer Because MSCs can migrate and localize to breast cancers, formation of MSC-breast cancer cell hybrids maybe a potential mechanism for generating breast CSCs (Rappa, et al., 2012).Fusion of M2 macrophages with cells from breast cancer cell lines MCF-7 and MDA-MB-231 in the presence of polyethylene glycol produces hybrids that show increased migration, invasion, and tumorigenicity and haveCD44 + CD24 -/low phenotype (Ding, et al., 2012).genes.Second, ALDH1A can metabolize and detoxify chemotherapeutics (Magni, Shammah et al. 1996).Due to this property, ALDH1A is known as a contributing factor to chemotherapy resistance of hematopoietic stem cells.
What is the difference between the three populations considered to be BCSCs?There is a population with the phenotype of CD44 + CD24 -, another with ALDH, and another with CD133.There are also Where are breast CSCs from?Breast CSCs are formed through these mechanisms.Some in vitro studies and clinical investigations suggest that breast CSCs are produced in vivo through the following 2 mechanisms: (1) accumulation of mutations in mammary stem cells during development that causes these cells to lose their selfrenewal capacity and (2) development of breast CSCs from non-stem cells through different evolutionary mechanisms.
CSCs in breast cancer cell lines was clearly recorded by Gupta et al. (2011).They sorted breast CSCs with stem-like basal and luminal phenotypes from 2 breast cancer cell lines SUM159 and SUM149and observed that these cells exhibited the properties of their parental cell lines after 11 days in culture(Gupta, Fillmore, Jiang, Shapira, Tao, Kuperwasser and Lander, 2011).In another study, Piggott et al. (2011) depleted CSCs from BT474 breast cancer cell line and observed that this depleted cell line re-established progenitor-like cells et al. also produced CSCs by transfecting non-CSCs withSV40andH-ras (Chaffer, et al., 2011).Some studies have shown that breast CSCs can be produced in vitro by fusing breast cancer cells with mesenchymal stromal cells or macrophages.Hybrids of bone marrow-derived mesenchymal stem cells (MSCs) and cells from 2 breast cancer cell lines MDA-MB-231 (MDA) and MA11 show increased metastatic capacity.

Figure 1 .
Figure 1.Relations of breast cancer stem cells and normal mammary stem cells.
ALDHs) are a group of enzymes that catalyze the oxidation (dehydrogenation) of aldehydes (Marchitti, Brocker et al. 2008).There are 19 kinds of ALDH identified in humans.One of these is ALDH1A, a well-known enzyme responsible for oxidizing aldehydes to carboxylic acids (Marchitti, Brocker et al. 2008).ALDH1A is highly expressed in the epithelium of testis, brain, eye, liver, kidney, and some stem cells.To date, ALDH1A exhibits two main functions in hematopoietic stem cells and neural stem cells.The first is the oxidation of retinal to retinoic acid (Collins 2008).The retinoic acid activates nuclear retinoic acid receptors (RARs) which in turn regulate the expression of related combinations of phenotypes such as CD44 + CD24 -, CD133 + , and ALDH + .Some populations of BCSCs also include phenotypesCD44 + CD133 + , CD44 + ALDH + , or CD133 + ALDH + .These differences seem to be related to distinct levels of differentiation status in BCSCs(Ricardo,   Vieira et al. 2011).

Figure 2 .
Figure 2. Breast cancer stem cells with different markers.

Figure 3 .
Figure 3. Strategies for breast cancer stem cell characterization and isolation high andCD24 low . ).