Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Paula, Arnaud Da Cruz; Lopes, Carlos

doi:10.21873/anticanres.11552

Cited by 42 publications

(24 citation statements)

References 85 publications

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“…The findings also excluded the possibility that CXCR2 could be used as a marker of CSC in non-TNBC, because CSC is considered to be a small subpopulation of cells within the tissue, typically ≤1%. 27 …”

Section: Resultsmentioning

confidence: 99%

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer

Wang¹,

Tu²,

Du³

et al. 2018

OTT

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BackgroundBreast cancer is the leading cause of mortality from cancer in women worldwide, and cancer stem-like cell (CSC) is responsible for failure treatment of breast cancer. It plays an important role in resistant disease and metastasis. CD44/CD24 and ALDH are well-accepted protein markers of breast CSC, and it was reported that distinct subtypes of breast CSC were identified by the 2 markers. It is possible that there are various kinds of breast CSC which could be identified by different markers, and CSC markers utilized at present are not enough to fully understand breast CSC. Finding out more novel CSC markers is necessary. CXCR2 is involved in breast cancer metastasis, treatment resistance, and recurrence and has positive cross-talk with known breast CSC protein markers. It can be concluded that CXCR2 is related to breast CSC, and further study is in need.ResultsIn this study, we assessed expression of CXCR2 with immunohistochemistry in breast cancer tissues from 37 patients and discovered that level of CXCR2 was significantly lower in triple-negative breast cancer (TNBC) compared with non-TNBC. CXCR2 expression decreased in estrogen receptor-negative or HER2-negative breast cancer, but not progesterone receptor-negative counterparts. By immunofluorescence, we observed high coexpression rate of CXCR2 and CSC-related proteins, including NANOG and SOX2. To prove our speculation that CXCR2 was a novel CSC marker for TNBC, we used 4T1 cell, which is a TNBC cell line, to analyze CXCR2-positive subpopulations and observed that CXCR2-positive 4T1 cells showed characteristics of CSC, including resistance to cisplatinum, radiation, and hypoxia, low proportion (around 1%), much more tumor xenografts, tumor spherule formation, and higher levels of CSC-related mRNA compared with CXCR2-negative cells.ConclusionCXCR2 is an acceptable and newly discovered CSC marker for only TNBC.

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Section: Resultsmentioning

confidence: 99%

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer

Wang¹,

Tu²,

Du³

et al. 2018

OTT

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“…Cancer stem cells (CSCs) have been demonstrated to play a critical role in the initiation of metastasis, while other studies have suggested that ALDH-positive cells exhibit stem cell-like properties, thus indicating a potential role in metastatic cascade (19)(20)(21). Also, it has been reported that both CD44 + /CD24and ALDH1 + breast cancer stem cells are enriched in TNBC and may contribute to chemotherapy resistance and tumor metastasis of TNBC (22,23). Interestingly, our previous work in glioblastoma (GBM) has suggested that ALDH1A3 and CD44 expression are correlated with the aggressive and radioresistant mesenchymal (MES) subtype as compared to the proneural (PN) subtype (24).…”

Section: Introductionmentioning

confidence: 99%

Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis–Initiating Cells

Yamashita

Minata

Ibrahim

et al. 2020

Molecular Cancer Therapeutics

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The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates; however, this has failed to positively affect the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial–mesenchymal transition (EMT) gene signature (mesenchymal markers, CD44 or Vimentin) were compared in tumors derived from BM, lung metastases (LM), or bone metastases (BoM) of patients as well as mice after injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small-molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.

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“…These are related to a small fraction of stem-like cells termed as cancer stem cells (CSCs) or tumour-initiating cells (TICs) that exhibit an aggressive phenotype [1]. Breast cancer stem cells (BCSCs) have been isolated from breast cancer cell lines and breast samples from cancer patients based on a CD44 high/+ CD24 low/− phenotype and/or high ALDH (aldehyde dehydrogenase) activity [2,3]. BCSCs play an essential role in tumorigenicity as well as local invasion and migration.…”

Section: Introductionmentioning

confidence: 99%

“…CD44 is responsible for control of numerous cellular functions, including cell adhesion, migration, homing, and transmission of growth signals [4,5,9]. Recent findings have shown that about 70% of breast cancer patients with early bone metastasis have tumours enriched in the CD44 + phenotype [3]. However, CD24 is poorly expressed in various cancer types and it is involved in cell adhesion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells

Ibiyeye

Zuki

2020

IJMS

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Cancer stem cells CSCs (tumour-initiating cells) are responsible for cancer metastasis and recurrence associated with resistance to conventional chemotherapy. This study generated MBA MD231 3D cancer stem cells enriched spheroids in serum-free conditions and evaluated the influence of combined doxorubicin/thymoquinone-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles. Single loaded drugs and free drugs were also evaluated. WST assay, sphere forming assay, ALDH activity analysis, Surface marker of CD44 and CD24 expression, apoptosis with Annexin V-PI kit, cell cycle analysis, morphological changes using a phase contrast light microscope, scanning electron microscopy, invasion assay and migration assay were carried out; The combination therapy showed enhanced apoptosis, reduction in ALDH activity and expression of CD44 and CD24 surface maker, reduction in cellular migration and invasion, inhibition of 3D sphere formation when compared to the free drugs and the single drug-loaded nanoparticle. Scanning electron microscopy showed poor spheroid formation, cell membrane blebbing, presence of cell shrinkage, distortion in the spheroid architecture; and the results from this study showed that combined drug-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles can efficiently destroy the breast CSCs compared to single drug-loaded nanoparticle and a simple mixture of doxorubicin and thymoquinone.

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Implications of Different Cancer Stem Cell Phenotypes in Breast Cancer

Abstract: Abstract. The

Cited by 42 publications

References 85 publications

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer

Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis–Initiating Cells

Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells

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