Stemness in Human Thyroid Cancers and Derived Cell Lines: The Role of Asymmetrically Dividing Cancer Stem Cells Resistant to Chemotherapy

Ma, Risheng; Minsky, Noga; Morshed, Syed A.; Davies, Terry F.

doi:10.1210/jc.2013-3545

Cited by 48 publications

(35 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These previous studies propose that stemness and aggressiveness of the pediatric cancer is related to EMT, which results in drug resistance, and consequently poor prognosis. Diverse mechanisms and molecules have been associated with poor clinical outcomes for advanced thyroid cancer [20,21]. In the current study, we focused on the relationship between drug resistance and EMT in pediatric thyroid cancer to explain the poor clinical outcomes [22].…”

Section: Introductionmentioning

confidence: 99%

Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

Kim

Park

et al. 2020

Cancers

View full text Add to dashboard Cite

The incidence of papillary thyroid carcinoma (PTC) has been increasing worldwide. PTC is the most common type of differentiated thyroid cancer and usually shows good prognosis. However, some PTC is driven to advanced stage by epithelial-mesenchymal transition (EMT)-mediated drug resistance, which is particularly noticeable in pediatric patients. There are limited options for systemic treatment, necessitating development of new clinical approaches. Here, we aimed to clarify genetic differences due to age of patients with PTC, and thereby aid in developing novel therapeutics. Patients with biochemically and histologically confirmed PTC were included in this study. PTC cells were acquired from young and older patients showing drug resistance, and were compared via microarray analysis. Cellular proliferation and other properties were determined after treatments with lenvatinib and sorafenib. In vivo, tumor volume and other properties were examined using a mouse xenograft model. Lenvatinib-treated group showed obvious suppression of markers of anti-apoptosis, EMT, and the FGFR signaling pathway, compared with control and Sorafenib-treated group. In the xenograft models, lenvatinib treatment induced significant tumor shrinkage and blocked the proto-oncogene Bcl-2 (B cell lymphoma/leukemia gene-2) and FGFR signaling pathway, along with reduced levels of EMT markers, compared with control and Sorafenib-treated group. Our findings clarify the age-dependent characteristics of pediatric PTC, giving insights into the relationship between young age and poor prognosis. Furthermore, it provides a basis for developing novel therapeutics tailored to the age at diagnosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

Kim

Park

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…4,5,12,18,23,25,28,31,36,37,39,40,[108][109][110] Figure 1 Diagrammatic illustration of epithelial to mesenchymal transition (EMT) and interaction of cancer stem cells (CSCs) with the tumor microenvironment. EMT is influenced by multiple factors and TGFβ-induced EMT is a useful experimental model.…”

mentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

show abstract

“…22 New biomarkers to identify thyroid CSCs, such as aldehyde dehydrogenase (ALDH) and stage-specific embryonic antigen 1 (SSEA1) expression, have also been identified. 23,24 Other studies have shown that thyroid CSCs could be generated from primary thyroid tumors in immunodeficient mice. 24 Herein, we characterized a series of thyroid cancer cell lines for CSC properties.…”

mentioning

confidence: 99%

Generation of Novel Thyroid Cancer Stem-Like Cell Clones

Hardin

Harrison

et al. 2016

The American Journal of Pathology

View full text Add to dashboard Cite

Anaplastic thyroid cancer is an aggressive and highly lethal cancer for which conventional therapies have proved ineffective. Cancer stem-like cells (CSCs) represent a small fraction of cells in the cancer that are resistant to chemotherapy and radiation therapy and are responsible for tumor reoccurrence and metastasis. We characterized CSCs in thyroid carcinomas and generated clones of CSC lines. Our study showed that anaplastic thyroid cancers had significantly more CSCs than well-differentiated thyroid cancers. We also showed that Aldefluor-positive cells revealed significantly higher expression of stem cell markers, self-renewal properties, thyrosphere formation, and enhanced tumorigenicity. In vivo passaging of Aldefluor-positive cells resulted in the growth of larger, more aggressive tumors. We isolated and generated two clonal spheroid CSC lines derived from anaplastic thyroid cancer that were even more enriched with stem cell markers and more tumorigenic than the freshly isolated Aldefluor-positive cells. Resveratrol and valproic acid treatment of one of the CSC lines resulted in a significant decrease in stem cell markers, Aldefluor expression, proliferation, and invasiveness, with an increase in apoptosis and thyroid differentiation markers, suggesting that these cell lines may be useful for discovering new adjuvant therapies for aggressive thyroid cancers. For the first time, we have two thyroid CSC lines that will be useful tools for the study of thyroid CSC targeted therapies.

show abstract

Stemness in Human Thyroid Cancers and Derived Cell Lines: The Role of Asymmetrically Dividing Cancer Stem Cells Resistant to Chemotherapy

Cited by 48 publications

References 37 publications

Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

Impact of Age-Related Genetic Differences on the Therapeutic Outcome of Papillary Thyroid Cancer

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Generation of Novel Thyroid Cancer Stem-Like Cell Clones

Contact Info

Product

Resources

About