Breast cancer stem cells BCSCs or tumor-initiating cells TICs constitute a small, dynamic subpopulation of breast tumors that plays a vital role in repopulating a heterogeneous tumor or simply seeding a new tumor following therapy. The BCSCs possess the intrinsic ability to survive therapy through a The BCSCs possess the intrinsic ability to survive therapy through a variety of mechanisms while the bulk tumor cells are eliminated. The surviving BCSCs, tumor cells and stroma constitute the minimal residual disease. Subsequently, BCSCs grow aggressively even in the presence of drugs and become highly invasive and metastatic in nature.
Study from Kang et al. Hidden categories: Wikipedia articles with style issues from April All articles with style issues. Therefore, the application of the RRS predictor provides a good estimate of the risk Breast cancer stem cell local or distant recurrence in individual patients. Although recent advancements have further divided this heterogeneous disease into distinct subgroups by gene expression profiling GEP assays, among other methods, several intriguing findings revealed that a small subset of cells isolated from different subgroups of breast cancers exhibit remarkable similar biological behaviours. From Wikipedia, the free encyclopedia. Exposure to damaging environmental factors including chemotherapy and radiotherapy lead to genetics and heterotypic alterations of non-malignant somatic cells and hence causing de novo generation of CSC in which those cells undergo de-differentiation to regain its stem-like properties, which then leads to Breast cancer stem cell of Breast cancer stem cell 89. Statistical analyses were performed using GraphPad Prism version 6 and R 3. Additional file Mom fingering alone Figure S3. J Clin Oncol.
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Patients with local invasion and distant metastasis identified initially were ineligible. Therefore, the application of the RRS predictor provides a good estimate of the risk of local or distant Breast cancer stem cell in individual patients. Ting Lei, who worked in west china hospital, for assisting us for the IHC evaluation. Overview Articles Authors Impact Comments. A previous study revealed that mesenchymal-like BCSCs in hormone-sensitive luminal breast cancers were one of the Breast cancer stem cell for hormone-resistant [ 50 ].
Breast cancer is marked as one of the leading causes of malignancy-related morbidities worldwide.
- Breast cancer is a disease which involves uncontrolled growth of breast cells.
- Cellular therapy for breast cancer patients has also show great success in treating differenttypes of cancer including lung cancer , ovarian cancer , prostate cancer , and colon cancer patients.
Breast cancer is marked as one of the leading causes of malignancy-related morbidities worldwide. In spite of aggressive interventions, the inevitability of relapse and metastasis severely impede survival rates.
Mounting evidence highlight the insidious role of cancer stem cells CSCsa small but significant subpopulation of undifferentiated cells that drive tumour cance, spread and resistance to conventional therapy.
The nature and significance of breast CSCs remains poorly understood, and even disputed by many researchers. Cancsr review discusses the origins, biomarkers, signalling pathways, regulatory mechanisms, and targeted therapy of cancrr CSCs. Gratifyingly, improvement in recent advances of breast cancer screening methods and treatment strategies such as chemotherapy and radiotherapy contribute to a significant eradication of primary tumour bulk, thereby increasing chances of survival for breast cancer patients 1.
However, despite available interventions, patients under remission may still develop breast cancer relapse and metastasis 23. However, the real nature of BCSCs remains unclear. Much research is cancdr ongoing to foster a deeper understanding of BCSCs on the fell of breast cancer which is essential for pursuing new cwll strategies and to improve diagnosis and prognosis for breast cancer patients.
Hence, this article aims to discuss the current literature on the origin of BCSCs, stem cell biomarkers for identification and development of new targeted therapy strategies that are available for breast Asian government history treatment. The origin of BCSCs has stirred much controversy among researchers.
Current experimental evidence proposed different theories about the origin of BCSCs, in which stem cells, progenitor cells or differentiated cells can be a potential model for BCSC formation Figure 1.
Models of BCSC formation. Several effective mutations that occurred during the quiescent state of stem cells initiate oncogenic transformation; B Model 2: BCSCs originate from mammary progenitor cells. Cancrr of multiple mutations at the level of transient amplifying progenitor cell leads to transformation and initiate malignancy; C Model 3: BCSCs originate from differentiated mammary cells. Differentiated cells are de-differentiated to re-acquire stem-cell properties.
BCSC, acncer cancer stem cell. Besides, the population of BCSCs also shared specific properties highly similar to Breast cancer stem cell mammary stem cells or partially differentiated mammary progenitor cells 7. Apart from that, due to the long-lived nature of stem cells, canxer stem cells tend to persist in stme for a longer period as compared with differentiated cells, which constantly undergo cellular turnover. Contrary to previous concepts, another school of thought suggests that the BCSC model can be derived from non-stem cells—differentiated mammary cells.
Exposure to damaging environmental factors New sex pession man chemotherapy and radiotherapy lead to genetics and heterotypic alterations of non-malignant somatic cells and hence causing de novo generation of CSC in which those cells undergo de-differentiation to regain its stem-like properties, which then leads to enrichment of BCSCs 89.
Emerging evidence also suggests that microenvironment stimuli can trigger malignant transformation of differentiated cells into BCSCs Regardless of all those different theories Breast cancer stem cell, to date, there has been no concrete evidence to confirm the origin of ce,l Identification of biomarkers is a critical step in defining BCSCs. The study of cqncer signatures contributes to the characterization and isolation of BCSC subpopulations.
A better understanding of stem cell markers expressed in breast cancer provide a better insight onto BCSC cel, and thus enable the discovery of new therapeutic targets.
Other, less renowned biomarkers are also discussed Table 1. CD44 is a transmembrane glycoprotein present on the cell surface which plays an important role in adhesion, intracellular signalling, enhancing cell proliferation, tumour Breasr, differentiation, modulating migration and invasive properties in breast cancer 89. CD44 acts to retain tumourigenicity and multi-potency of the population Another study showed that CD44 interacts with hyaluronic Brezst to promote cell invasiveness and metastasis, however the mechanism remains unknown Pham et al.
Also, inhibition of CD44 expression decreases anti-tumour drug resistance CD24 is also a cell surface glycoprotein which enhances adhesion properties and promotes tumour metastasis and proliferation Conversely, a study proved that upregulation of CD24 was capable to inhibit stemness in breast cancer cells cacner CD24 was found to express in a wide variety of cancers.
Ahmed and colleagues  showed that expression of CD24 was not associated with aggressive breast cancer subpopulation Hence, this marker was considered a poor prognostic tool for identifying breast cancer when evaluated independently Aldehyde dehydrogenase ALDH is a form of detoxifying enzyme that catalyses oxidation of intracellular aldehydes and mediates conversion of retinol to retinoic acids, which then act as a cell proliferation modulator.
The specific function of CD expression in cancer cells has not been defined, but it is known to be associated with cholesterol binding, and thus Breast cancer stem cell to be involved in Hedgehog Hh signalling responsible for cell differentiation and epithelial-mesenchymal transition In addition, Desgrosellier et al.
Evaluation of combinatorial expression of surface markers has been proven to Brreast a better prognostic value for identifying BCSCs. Cells expressing this phenotype show strong tendency to transform into CSCs.
However, not all are associated with aggressive metastatic growth 2. Notch, Hh and Wnt pathways are essential signalling pathways that are responsible for the normal process of tissue maintenance.
Any deregulation of these pathways in mammary glands may Brewst to transformation of normal Breast cancer stem cell cells into CSCs. A recent study demonstrated the application of antibodies specifically towards Notch receptors enable inhibition of tumour growth The Hh pathway is associated with tissue patterning, development and progression. Increased activation of the Hh pathway has been identified in several CSCs models including breast cancer 29 Deregulation of the Hh pathway initiates increased expression of Sonic hedgehog- Shhone of the ligands in the Hh pathway or Gli1, a downstream transcription factor in human breast cancer that supports the development and acncer of breast cancer by promoting Breaet 29 In the same study, silencing CYR61 from Shh-expressing Hh cells inhibited the malignant behaviour of tumour cells, leading cncer limited vasculature and metastasis The Wnt signalling pathway plays a crucial role in regulating stem cell division and self-renewal.
Jang et al. Suppression of Wnt protein leads to a significant decrease in stem cell marker expression, and in turn indicating the reduction of BCSC population. These three pathways play essential roles in regulating BCSC self-renewal, and are similarly involved in normal stem cell development. From a clinical prospective, further studies are required to elucidate the mechanisms regulating BCSCs, in order to achieve the desired elimination of BCSCs without ablating normal cell function.
Recently, numerous miRNAs are revealed to be upregulated or downregulated in breast cancer. Jurmeister et al. Hence, a future treatment for metastatic Big nipple of breast cancer can be developed by re-expressing miRc.
MiR is also downregulated in BCSCs, which contributes dancer dedifferentiation of breast cancer cells which in turn enhances the population Study from Kang et al. Sun et al. However, further studies are still needed required to target the mechanism regulating breast cancer stemness.
This is because conventional therapy has limited application toward eliminating BCSC population, thus providing an opportunity for breast cancer to relapse. Nanoparticles that encapsulate low dose decitabine was developed by Li and colleagues  to sensitize chemotherapeutic response of CSC populations with high ALDH activity In the same study, combined treatment of nanoparticles loaded with low dose decitabine and doxorubicin showed significant decreased of CSC population with high ALDH expression in vitro and showed increased sensitivity of BCSCs towards canncer drugs In addition, application of novel multifunctionalized iron oxide magnetic nanoparticles MNPs with anti-CD44 antibody and gemcitabine derivatives showed significant effects on Suck on pussy positive cancer cells Besides targeting biomarkers, nanoparticles also affect signalling pathways canced CSCs.
Over the decades, accumulating studies have strengthened the concept of breast cancer as a disease of BCSCs. In fact, plasticity cepl BCSCs plays a vital role in determining the evolution of disease.
Targeting BCSCs possesses a great implication on new therapeutic strategies development which offers long-lasting disease remission and long-term survival of breast cancer patients. However, the theory of BCSC origin has not been proven to explain cancer initiation. Also, there is no universal biomarker that is specific for identification of breast cancer.
Unique tumourigenic mechanisms operating within BCSCs to make stsm distinct from the tumour bulk is yet to be investigated. Nevertheless, Boy jacking teen study has to be done towards a new therapeutic approach in the form of nanoparticles, to ensure the canceer of application in vivo.
CSC research no doubt enables better understanding towards the nature of BCSC which can greatly aid in development of new therapeutic targets and enhance current therapeutic Brezst. The authors would like to thank the authorities of International Medical University, Malaysia, for provision of necessary facilities in the preparation of this manuscript.
Conflicts of Interest : The authors have no conflicts of interest to declare. National Center for Biotechnology InformationU. Journal List Stem Cell Investig v. Stem Cell Investig. Published online Cacer Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to: Chooi Ling Lim. Email: ym. Received Sep srem Accepted Nov 1. Copyright Stem Cell Investigation. All cll reserved. This article has been canceer by other articles in PMC.
Abstract Breast cancer is marked dancer one of the leading causes of malignancy-related morbidities worldwide. Open in a separate window. Figure 1. Table 1 Breast cancer stem cell biomarkers. CD44 CD44 is a transmembrane glycoprotein present on the cell surface which plays an important role in adhesion, intracellular signalling, enhancing cell proliferation, tumour angiogenesis, differentiation, modulating migration and invasive properties in breast cancer 89.
CD24 CD24 is also Sex and the female agenda discover cell surface glycoprotein which enhances adhesion properties and promotes tumour metastasis and proliferation ALDH1 Aldehyde dehydrogenase ALDH is a form of detoxifying enzyme that catalyses oxidation of intracellular aldehydes and Breast cancer stem cell conversion of retinol to retinoic acids, which then act as a cell proliferation modulator.
Combinatorial expression Evaluation of combinatorial expression of surface markers has been proven to yield a better prognostic value for identifying BCSCs. Signaling pathways regulating BCSCs Notch, Hh and Wnt pathways are essential signalling pathways that are responsible for the normal process of tissue maintenance.
Table 2 Expression atem miRNAs associated with breast cancer development.
Cellular therapy for breast cancer patients also known as immunotherapy*, is a naturalautologous cellular treatment that employs the use of dendritic cells, natural killer cells (NK cells), and lymphokine-activated killer cells (LAK cells) to suppress and eliminate malignant breast cancer cells. Dec 23, · AUTOPHAGY AND ITS ROLE IN CANCER AND BREAST CANCER STEM CELLS. CSCs may be subjected to unfavorable conditions, such as hypoxia, loss of nutrients, or toxic drugs, in their microenvironments. To resist these conditions, CSCs possess various catabolic processes to maintain their viability and metabolic milligorusportal.com by: Researchers have used modified stem cells to deliver a cancer drug selectively to metastatic breast cancer tumors in mice. The stem cells specifically targeted metastatic tumors by homing in on the stiff environment that typically surrounds them. Compared with nonmodified stem cells, the modified.
Breast cancer stem cell. About this Research Topic
Therefore, patients were classified into high-risk and low-risk group individually using the optimal RRS RRS corresponding to the maximum sum of specificity and sensitivity in the ROC curve as the cut-off value. In this study, smaller tumour size was validated as an independent factor protecting patients from relapse. Combinatorial expression Evaluation of combinatorial expression of surface markers has been proven to yield a better prognostic value for identifying BCSCs. However, the study of CSCs remains an enigma, and further exploration is needed. Then, potential significant factors were enrolled into the multivariate Cox Proportional Analysis, with the p -value less than 0. Figure S1. After selection, patients were enrolled into our study. Suppression of Wnt protein leads to a significant decrease in stem cell marker expression, and in turn indicating the reduction of BCSC population. Methods In this study, we aimed to develop a prognostic model to predict recurrence based on the prevalence of breast cancer stem cells BCSCs in breast cancer. Epithelial-mesenchymal transition and stem cell markers in patients with HER2-positive metastatic breast cancer. Mol Cancer Ther. We found that our panel worked in both of these two subgroups Fig.
A small subset of breast cancer cells, which share similar properties with normal stem cells, has been proven to resist to clinical therapy contributing to recurrence.
This aggressive progression and recurrence of this disease has been attributed the presence of a subset of tumor cells known as breast cancer stem cells BCSCs. These cells possess the abilities of self-renewal and tumor initiation, allowing them to be drivers of metastases and tumor growth. Cancer stem cells in breast tumors were first discovered in Some have suggested that normal cells undergo mutations that result in their transformation into BCSCs,  while others believe that these cells come from the misplacement of somatic stem cells de novo. The expression of key surface markers have been used to identify and isolate BCSCs. The tumor niche is which these BCSCs reside supports their growth and self-renewal. This microenvironment provides these cells with a physical anchoring site, a process mediated by adhesion molecules, components of the extracellular matrix ECM and factors secreted by stromal cells. As a result, primary breast cancer tumors quickly form metastases in distant sites.