scholarly journals LPA/PKD-1 signaling promotes development of arteriolar niche that supports self-renewal of breast cancer stem cells and stemness

2020 ◽  
Author(s):  
Yinan Jiang ◽  
Yichen Guo ◽  
Jinjin Hao ◽  
Rachael Guenter ◽  
Justin Lathia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Regulatory Mechanisms ◽  
Cancer Growth ◽  
Breast Cancer Stem Cells ◽  
Self Renewal ◽  
Estrogen Receptor Positive

ABSTRACTBreast cancer stem cells (BCSCs) are essential for cancer growth, metastasis and recurrence. However, the regulatory mechanisms of self-renewal and interactions with the vascular niche within tumor microenvironment are currently under investigation. Here, we demonstrate that BCSCs are enriched within arteriolar niche within the tumor microenvironment of estrogen receptor positive (ER+) BC and bi-directionally interact with arteriolar endothelial cells (ECs). Mechanistically, this interaction is driven by the LPA/PKD-1 signaling pathway, which promotes arteriolar differentiation and self-renewal. Furthermore, this pathway directly promotes stemness features. These findings suggest that targeting LPA/PKD-1 signaling may disrupt the arteriolar niche within the tumor microenvironment and concomitantly eradicate BCSCs, thereby attenuating BC progression.

scholarly journals Targeting the Roots of Recurrence: New Strategies for Eliminating Therapy-Resistant Breast Cancer Stem Cells

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 54
Author(s):  
Margaret L. Dahn ◽  
Paola Marcato
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Self Renewal ◽  
New Strategies

Cancer stem cells (CSCs) are functionally defined in our laboratories by their impressive tumor-generating and self-renewal capacity; clinically, CSCs are of interest because of their enhanced capacity to evade conventional therapies [...]

scholarly journals Let-7c blocks estrogen-activated Wnt signaling in induction of self-renewal of breast cancer stem cells

2016 ◽  
Vol 23 (4) ◽  
pp. 83-89 ◽  
Author(s):  
X Sun ◽  
C Xu ◽  
S-C Tang ◽  
J Wang ◽  
H Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Breast Cancer Stem Cells ◽  
Self Renewal

scholarly journals The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1028 ◽  
Author(s):  
David Rodriguez ◽  
Marc Ramkairsingh ◽  
Xiaozeng Lin ◽  
Anil Kapoor ◽  
Pierre Major ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor ◽  
Cancer Stem Cells ◽  
Hormone Therapy ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Therapy Resistance ◽  
Breast Cancer Stem Cells ◽  
Er Positive

Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance.

scholarly journals The anti-diabetic drug metformin suppresses self-renewal and proliferation of trastuzumab-resistant tumor-initiating breast cancer stem cells

2010 ◽  
Vol 126 (2) ◽  
pp. 355-364 ◽  
Author(s):  
Alejandro Vazquez-Martin ◽  
Cristina Oliveras-Ferraros ◽  
Sonia Del Barco ◽  
Begoña Martin-Castillo ◽  
Javier A. Menendez
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Self Renewal

scholarly journals PDGF-AB rich-trombocyte lysate supplementation from breast cancer patients increased the proliferation of breast cancer stem cells

2018 ◽  
Vol 27 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Wiwi A. Kartolo ◽  
Jeanne A. Pawitan ◽  
Alida R. Harahap ◽  
Septelia I. Wanandi
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Platelet Lysate ◽  
Population Doubling ◽  
Population Doubling Time ◽  
Breast Cancer Stem Cells ◽  
Platelet Counts ◽  
Healthy Donors

Background: Thrombocytosis in breast cancer (BC) patient was thought to play a role in the invasiveness of breast cancer stem cells (BCSCs). Modification of tumor microenvironment was proposed to increase the efficacy of anticancer therapy. This study was aimed to analyze the effect of platelet lysate (PL) as well as its PDGF-AB content as a tumor microenvironment on (CD24-/CD44+) BCSC proliferation.Methods: This was an experimental study that treated culture of BCSCs with PL from breast cancer (BC) patients or healthy donors. Venous blood from all subjects were subjected to prior hematology test and then processed to obtain platelet rich plasma  (PRP). Platelet counts in PRP were determined. PRP was processed to obtain PL. PDGF-AB contents in PL were measured. PL at concentrations of 0.01% (v/v) was supplemented into DMEM-F12 medium and used for culturing BCSCs (CD24-/CD44+ cells). After 48 hours, total cell count, population doubling time (PDT), and cell viability were calculated and their correlation with platelet count and PDGF-AB levels were analyzed.Results: BC patients (n=5) had higher platelet counts and PDGF-AB levels in PL compared to healthy donors (n=15), (p=0.02). PL from BC patients could stimulate the proliferation of BCSCs higher than healthy donors (p<0.001) and showed lower PDT value (p=0.001). Cell proliferation and PDT showed strong correlation with PDGF-AB level. This observation suggests that PDGF-AB has a role on BCSCs proliferation. PL showed no effect on BCSCs viability.Conclusion: Breast cancer patient platelet lysate stimulated BCSC proliferation.

scholarly journals Loss of SIRT4 promotes the self-renewal of Breast Cancer Stem Cells

Theranostics ◽  
2020 ◽  
Vol 10 (21) ◽  
pp. 9458-9476 ◽  
Author(s):  
Lutao Du ◽  
Xiaoyan Liu ◽  
Yidan Ren ◽  
Juan Li ◽  
Peilong Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
The Self ◽  
Breast Cancer Stem Cells ◽  
Self Renewal
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