Cancer Stem Cells in Breast: Current Opinion and Future Challenges

Charafe-Jauffret, Emmanuelle; Monville, Florence; Ginestier, Christophe; Dontu, Gabriela; Birnbaum, Daniel; Wicha, Max S.

doi:10.1159/000123845

Cited by 155 publications

(102 citation statements)

References 141 publications

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“…[1][2][3] It is reported that BCSCs play a key role in radio and chemo therapy resistance. Based on these observations, the BCSCs have become the foundation for new preventive and therapeutic strategies in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Xu¹,

Sun²,

Qin

et al. 2015

Cell Cycle

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Keywords: breast cancer stem cells, KRas, let-7a, mammosphere formation capacity, MAPK/ERK, NF-kB Abbreviations: BCSCs, breast cancer stem cells; MFE, mammosphere-forming efficiency Breast cancer stem cells (BCSCs) have the greatest potential to maintain tumorigenesis in all subtypes of tumor cells and were regarded as the key drivers of tumor. Recent evidence has demonstrated that BCSCs contributed to a high degree of resistance to therapy. However, how BCSCs self renewal and tumorigenicity are maintained remains obscure. Herein, our study illustrated that overexpression of let-7a reduced cell proliferation and mammosphere formation ability of breast cancer stem cells(BCSCs) in a KRas-dependent manner through different pathways in vitro and in vivo. To be specific, we provided the evidence that let-7a was decreased, and reversely the expression of KRas was increased with moderate expression in early stages (I/II) and high expression in advanced stages (III/IV) in breast cancer specimens. In addition, the negative correlation between let-7a and KRas was clearly observed. In vitro, we found that let-7a inhibited mammosphere-forming efficiency and the mammosphere-size via NF-kB and MAPK/ERK pathway, respectively. The inhibitory effect of let-7a on mammosphere formation efficiency and the size of mammospheres was abolished after the depletion of KRas. On the contrary, enforced expression of KRas rescued the effect of let-7a. In vivo, let-7a inhibited the growth of tumors, whereas the negative effect of let-7a was rescued after overexpressing KRas. Taken together, our findings suggested that let-7a played a tumor suppressive role in a KRas-dependent manner.

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Section: Introductionmentioning

confidence: 99%

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Xu¹,

Sun²,

Qin

et al. 2015

Cell Cycle

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“…Mammosphere formation is a functional assay because it exploits the unique property of stem-like/ progenitor cells to survive and grow in serum-free suspension, while more differentiated cells undergo anoikis and die in these conditions 35,36 . However, because a reduction in mammosphere formation may represent (i) increased apoptosis, (ii) decreased proliferation of early progenitor cells or stem cells, (iii) a reduction in stem cell self-renewal, or (iv) interference with anchorage-independent growth, it is best used in conjunction with other anti-CSC assays.…”

Section: Cd24mentioning

confidence: 99%

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Kastrati

Delgado-Rivera

Georgieva

et al. 2017

JoVE

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Inflammation is a cancer hallmark that underlies cancer incidence and promotion, and eventually progression to metastasis. Therefore, adding an anti-inflammatory drug to standard cancer regiments may improve patient outcome. One such drug, aspirin (acetylsalicylic acid, ASA), has been explored for cancer chemoprevention and anti-tumor activity. Besides inhibiting the cyclooxygenase 2-prostaglandin axis, ASA's anticancer activities have also been attributed to nuclear factor ĸB (NFĸB) inhibition. Because prolonged ASA use may cause gastrointestinal toxicity, a prodrug strategy has been implemented successfully. In this prodrug design the carboxylic acid of ASA is masked and additional pharmacophores are incorporated.This protocol describes how we synthesized an aspirin-fumarate prodrug, GTCpFE, and characterized its inhibition of the NFĸB pathway in breast cancer cells and attenuation of the cancer stem-like properties, an important NFĸB-dependent phenotype. GTCpFE effectively inhibits the NFĸB pathway in breast cancer cell lines whereas ASA lacks any inhibitory activity, indicating that adding fumarate to ASA structure significantly contributes to its activity. In addition, GTCpFE shows significant anti-cancer stem cell activity by blocking mammosphere formation and attenuating the cancer stem cell associated CD44 + CD24-immunophenotype. These results establish a viable strategy to develop improved anti-inflammatory drugs for chemoprevention and cancer therapy.

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“…These stem cells have the ability to self-renew and to develop into all the cells that form the tumour mass and are called cancer stem cells (CSCs) [5] . In the CSCs hypothesis, cancer derives from normal stem cells that are transformed into tumour cells [6] . Adult stem cells are characterized as long-living with a low proliferative rate and are exposed for prolonged periods to agents that can induce damage and can accumulate mutations that result in neoplastic transformation [7] .…”

Section: The New Hypothesis: Cancer Stem Cellsmentioning

confidence: 99%

“…Contrary to the "stochastic" model of tumorigenesis, for which the neoplastic transformation would result from random mutations incurred by a healthy cell that, consequently, undergoes clonal expansion. The CSCs hypothesis argues that the tumour begins from a stem cell, probably due to a dysregulation of the pathways involved in self-renewal [6] . However, these mechanisms are not exclusive and we can consider that other mechanisms can participate in the genesis and tumour progression, contributing to the heterogeneity of the tumour.…”

Section: The New Hypothesis: Cancer Stem Cellsmentioning

confidence: 99%

“…The principal MDR proteins that are expressed in BCSCs are the P-glycoprotein, the multidrug-resistance protein 1 (MDR1) and the cluster differentiation 243 (CD243). Chemotherapy drugs with anti-proliferative effects are less effective on CSCs population, because these cells divide less frequently than cancer cells [6,7] . For these reasons chemotherapy destroy many neoplastic cells but does not affect the minority component of tumour such as BCSCs.…”

Section: Breast Cancer Stem Cellsmentioning

confidence: 99%

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Role of nuclear receptors in breast cancer stem cells

Papi

Orlandi

2016

WJSC

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The recapitulation of primary tumour heterogenity and the existence of a minor sub-population of cancer cells, capable of initiating tumour growth in xenografts on serial passages, led to the hypothesis that cancer stem cells (CSCs) exist. CSCs are present in many tumours, among which is breast cancer. Breast CSCs (BCSCs) are likely to sustain the growth of the primary tumour mass, as well as to be responsible for disease relapse and metastatic spreading. Consequently, BCSCs represent the most significant target for new drugs in breast cancer therapy. Both the hypoxic condition in BCSCs biology and proinflammatory cytokine network has gained increasing importance in the recent past. Breast stromal cells are crucial components of the tumours milieu and are a major source of inflammatory mediators. Recently, the antiinflammatory role of some nuclear receptors ligands has emerged in several diseases, including breast cancer. Therefore, the use of nuclear receptors ligands may be a valid strategy to inhibit BCSCs viability and consequently breast cancer growth and disease relapse.

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Cancer Stem Cells in Breast: Current Opinion and Future Challenges

Cited by 155 publications

References 141 publications

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Role of nuclear receptors in breast cancer stem cells

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Cancer Stem Cells in Breast: Current Opinion and Future Challenges

Cited by 155 publications

References 141 publications

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Let-7a regulates mammosphere formation capacity through Ras/NF-κB and Ras/MAPK/ERK pathway in breast cancer stem cells

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NF&#954;B Activity and Breast Cancer Stem Cells

Role of nuclear receptors in breast cancer stem cells

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Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells