Metastasis is impaired by endothelial-specific Dll4 loss-of-function through inhibition of epithelial-to-mesenchymal transition and reduction of cancer stem cells and circulating tumor cells

2019 ◽  
Vol 36 (4) ◽  
pp. 365-380 ◽  
Author(s):  
Liliana Mendonça ◽  
Alexandre Trindade ◽  
Catarina Carvalho ◽  
Jorge Correia ◽  
Marina Badenes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

scholarly journals Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769591 ◽  
Author(s):  
Sheefa Mirza ◽  
Nayan Jain ◽  
Rakesh Rawal
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Stem Cells ◽  
Mesenchymal Transition ◽  
Lung Cancer Stem Cells

Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial–mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(−) population in circulation not only exhibit stem cell–related genes but also possess epithelial–mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell–based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

scholarly journals Prognostic value of cancer stem cells, epithelial-mesenchymal transition and circulating tumor cells in lung cancer

2013 ◽  
Vol 29 (5) ◽  
pp. 1763-1768 ◽  
Author(s):  
G. PIROZZI ◽  
V. TIRINO ◽  
R. CAMERLINGO ◽  
A. LA ROCCA ◽  
N. MARTUCCI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prognostic Value ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Interplay between Metabolism Reprogramming and Epithelial-to-Mesenchymal Transition in Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1973
Author(s):  
Yoann Daniel ◽  
Elise Lelou ◽  
Caroline Aninat ◽  
Anne Corlu ◽  
Florian Cabillic
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Mesenchymal Transition ◽  
Energy Needs ◽  
New Strategies ◽  
Pro Inflammatory Cytokines

Tumor cells display important plasticity potential, which contributes to intratumoral heterogeneity. Notably, tumor cells have the ability to retrodifferentiate toward immature states under the influence of their microenvironment. Importantly, this phenotypical conversion is paralleled by a metabolic rewiring, and according to the metabostemness theory, metabolic reprogramming represents the first step of epithelial-to-mesenchymal transition (EMT) and acquisition of stemness features. Most cancer stem cells (CSC) adopt a glycolytic phenotype even though cells retain functional mitochondria. Such adaptation is suggested to reduce the production of reactive oxygen species (ROS), protecting CSC from detrimental effects of ROS. CSC may also rely on glutaminolysis or fatty acid metabolism to sustain their energy needs. Besides pro-inflammatory cytokines that are well-known to initiate the retrodifferentiation process, the release of catecholamines in the microenvironment of the tumor can modulate both EMT and metabolic changes in cancer cells through the activation of EMT transcription factors (ZEB1, Snail, or Slug (SNAI2)). Importantly, the acquisition of stem cell properties favors the resistance to standard care chemotherapies. Hence, a better understanding of this process could pave the way for the development of therapies targeting CSC metabolism, providing new strategies to eradicate the whole tumor mass in cancers with unmet needs.

Harnessing the BMP signaling pathway to control the formation of cancer stem cells by effects on epithelial-to-mesenchymal transition

2017 ◽  
Vol 45 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Ashish Bosukonda ◽  
William D. Carlson
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Bmp Signaling ◽  
Human Breast ◽  
Self Renewal ◽  
Breast Cscs ◽  
Mesenchymal Transition

Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway. Furthermore, the compound is capable of blocking transforming growth factor-β induced epithelial-to-mesenchymal transition (EMT) in primary tumor cells, a critical step for tumor progression and metastasis. In addition, we have investigated the effects of P123 on self-renewal, growth, differentiation (reversal of EMT) and apoptosis of isolated human breast CSCs. We have shown that P123 and BMP-7 reverse the EMT process in human breast CSCs, and inhibit self-renewal and growth. Moreover, compared with single treatment with paclitaxel, co-treatment with paclitaxel and P123 showed an increase in cell apoptosis. Together, these findings suggest that P123 has the therapeutic potential to suppress both bulk tumor cells and CSCs. We believe that P123 represents a new class of drugs that have the potential to eliminate the primary tumor, prevent reoccurrence and metastasis, and enhance the treatment of breast cancer.

scholarly journals Circulating tumor cells and circulating cancer stem cells and their detection by the method of flow cytometry

2021 ◽  
Vol 66 (3) ◽  
pp. 370-384
Author(s):  
T. A. Pozniak ◽  
A. Y. Hancharou ◽  
V. M. Abashkin ◽  
A. I. Stanovaya ◽  
A. V. Prokhorov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Cancer Stem Cells ◽  
Early Diagnosis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Specific Cell ◽  
Early Stage Disease ◽  
Recurrent Cancer ◽  
Mesenchymal Transition

This review describes the circulating cancer stem cells (CCSCs) and circulating tumor cells (CTCs). CCSCs are one of the main initiators of recurrent cancer and thus make them an important target for the development of new treatment methods. CTCs are relatively new biomarkers for the early diagnosis of metastasis. CTCs provide doctors with valuable information about each stages of cancer treatments: diagnostic of early-stage disease, early detection of recurrent cancer, the efficiency of chemotherapy, and makes it possible to select an individual sensitive drug.The most informative and frequently used markers for the detection of CSCs and CSCs were described. The mechanism of two models of tumor formation is considered: clonal and hierarchical. The known mechanisms of epithelial-mesenchymal transition of tumor cells are described. The most widely used specific cell surface markers for the detection and isolation of CTCs and CCSCs are described. The efficiency of a sensitive high-precision method of multicolor flow cytometry using specific fluorescent dye-labeled monoclonal antibodies for the detection of CCSCs and CTCs in the blood of cancer patients is analyzed. Detection of CTCs and CCSCs provides important information for the early diagnosis of metastasis and open a possibility to personalized treatment, and to monitoring of all stages cancers.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1385
Author(s):  
Hyeon-Yeol Cho ◽  
Jin-Ha Choi ◽  
Joungpyo Lim ◽  
Sang-Nam Lee ◽  
Jeong-Woo Choi
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Cancer ◽  
Cancer Prognosis ◽  
Optical Biosensors ◽  
Diagnosis And Prognosis ◽  
Noise Factors ◽  
Prediction Of Relapse

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

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