scholarly journals Alterations in mitochondrial function and energy metabolism-related properties in thyroid cancer stem cells

Author(s):  
Yu Ren ◽  
Hongyu Liang ◽  
Xiao Wang ◽  
Zhongwei Cao ◽  
Yuzhen Ma ◽  
...  

Increasing evidence indicates that cancer stem cells (CSCs) are initiators of the occurrence, development, and recurrence of malignant tumors. Mitochondria are important organelles in eukaryotic cells, not only responsible for converting part of energy released during nutrients oxidation into the energy-yielding molecule adenosine triphosphate (ATP) to fuel the activities of cell, but also play essential roles in processes such as cell apoptosis and cellular proliferation. The mitochondrial-related abnormalities have also been considered to have an important role in the origin and development of tumors. This study aimed at testing the abnormalities in mitochondrial function and energy/metabolism-related phenotypes in thyroid cancer stem cells (TCSCs). TCSCs were isolated and identified from MDA-T32 thyroid carcinoma cell line. The mitochondrial mass and mitochondrial arrangement, amount of mitochondrial DNA (mtDNA), mitochondrial membrane potential (MMP), oxygen/glucose consumption, and intracellular concentrations of reactive oxygen species (ROS) and ATP levels were examined. Perinuclear mitochondrial distribution, low amount of mtDNA and oxygen/glucose consumption, high MMP, and low intracellular ROS and ATP concentrations were observed in TCSCs. Alterations in mitochondrial function and cellular energy metabolism may be used as novel indicators of thyroid cancer.

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Felipe de Almeida Sassi ◽  
Algemir Lunardi Brunetto ◽  
Gilberto Schwartsmann ◽  
Rafael Roesler ◽  
Ana Lucia Abujamra

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.


2020 ◽  
Vol 7 ◽  
Author(s):  
Cihan Zamur ◽  
Uğur Topal ◽  
Harun Özdemir ◽  
Serdar Altınay

The most frequently diagnosed endocrine cancer, which causes more deaths than any other endocrine cancer, is thyroid cancer. Cancer stem cells are rare cells found in tumors that can regenerate themselves, phenotypically leads to various tumor cell populations and trigger tumorigenesis. Cancer stem cells have been identified in many cancers, including thyroid cancer. Having an understanding of the molecular mechanisms which control the biology of cancer stem cells and the disease processes will help us in designing more rational targeted therapies for aggressive thyroid cancers. In this review, we aimed to present the current accepted knowledge about thyroid stem cells, information regarding the cellular origin of thyroid cancer stem cells, and the clinical results of cancer stem cells present in the thyroid gland.


2020 ◽  
Vol 21 (15) ◽  
pp. 5276 ◽  
Author(s):  
Ge Liu ◽  
Qing Luo ◽  
Hong Li ◽  
Qiuping Liu ◽  
Yang Ju ◽  
...  

Cancer stem cells (CSCs) are considered to be the main cause of tumor recurrence, metastasis, and an unfavorable prognosis. Energy metabolism is closely associated with cell stemness. However, how the stemness of liver cancer stem cells (LCSCs) is regulated by metabolic/oxidative stress remains poorly understood. In this study, we compare the metabolic differences between LCSCs and the hepatocellular carcinoma cell line HCCLM3, and explore the relationship between metabolism and LCSC stemness. We found that LCSCs from the hepatocellular carcinoma cell HCCLM3 exhibited more robust glucose metabolism than HCCLM3, including glycolysis, oxidative phosphorylation (OXPHOS), and pyruvate produced by glycolysis entering mitochondria for OXPHOS. Moreover, 2-deoxy-D-glucose (2-DG) enhanced the LCSC stemness by upregulating OXPHOS. In contrast, Mdivi-1 reduced the levels of OXPHOS and weakened the stemness by inhibiting mitochondrial fission. Together, our findings clarify the relationship between energy metabolism and LCSC stemness and may provide theoretical guidance and potential therapeutic approaches for liver cancer.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Arif Malik ◽  
Misbah Sultana ◽  
Aamer Qazi ◽  
Mahmood Husain Qazi ◽  
Gulshan Parveen ◽  
...  

Cancer originates from genetic mutations accumulation. Cancer stem cells have been depicted as tumorigenic cells that can differentiate and self-renew. Cancer stem cells are thought to be resistant to conventional therapy like chemotherapy and radiation therapy. Radiation therapy and chemotherapy damage carcinomic DNA cells. Because of the ability of cancer stem cells to self-renew and reproduce malignant tumors, they are the subject of intensive research. In this review, CSCs radioresistant mechanisms which include DNA damage response and natural radiosensitizers have been summed up. Reactive oxygen species play an important role in different physiological processes. ROS scavenging is responsible for regulation of reactive oxygen species generation. A researcher has proved that microRNAs regulate tumor radiation resistance. Ionizing radiation does not kill the cancer cells; rather, IR just slows down the signs and symptoms. Ionizing radiation damages DNA directly/indirectly. IR is given mostly in combination with other chemo/radiotherapies. We briefly described here the behavior of cancer stem cells and radioresistance therapies in cancer treatment. To overcome radioresistance in treatment of cancer, strategies like fractionation modification, treatment in combination, inflammation modification, and overcoming hypoxic tumor have been practiced. Natural radiosensitizers, for example, curcumin, genistein, and quercetin, are more beneficial than synthetic compounds.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14068-e14068
Author(s):  
Regina R. Miftakhova ◽  
Almaz Akhunzyanov ◽  
Julia V Filina ◽  
Svetlana F Khaiboullina ◽  
Albert A Rizvanov

e14068 Background: Deregulated cellular metabolism is characteristic for cancer cells which heavily rely on glycolysis to meet metabolic demands. Studies have shown that increased glucose metabolism promotes tumor cell survival through mechanisms related to mitochondrial activities. Recently, mitochondrial inhibitors have been proposed as a potential anticancer therapeutics. In 2015 Lamb et al. presented anti-cancer activity of several antibiotics targeting mitochondrial function. Interestingly, these drugs have the highest inhibitory effect on cancer stem cells (CSCs), a small population of cancer initiating cells. It is believed that tumor microenvironment plays significant role in maintaining CSC population. The hypoxia is a major feature of the tumor microenvironment contributing into CSC phenotype, tumorigenicity and metastasis. Therefore, we sought to determine the effect of five antibiotics targeting mitochondrial function on CSC survival in hypoxia conditions. Methods: MCF-7 cells were cultured in normoxic (20% O2) and hypoxic (4% O2) conditions for 14 days in a presence of azithromycin, doxycycline, tetracycline, erythromycin and chloramphenicol. The ability to form mammospheres was used to determine CSC survival. Results: Incubation of CSCs with erythromycin, doxycycline, tetracycline and chloramphenicol reduced the number of mammospheres, the decrease in mammosphere number was comparable for MCF-7 cells incubated under normoxic and hypoxic conditions [erythromycin (62.5 % ± 10.8% vs. 58.9% ± 2.2% ), doxycycline (75.2% ± 5.9% vs. 68.5% ± 5.4% ), tetracycline (56.0% ± 3.2% vs. 65.0% ± 15.0%) and chloramphenicol (71.5% ± 6.7% vs. 73.7% ± 5.5%)]. Interestingly, azithromycin did not show inhibiting activity on sphere formation under hypoxic condition, while number of spheres was reduced in normoxic conditions Conclusions: These data indicate that four out of five antibiotics in our study can be potentially applied for targeted eradication of breast CSCs in hypoxiс conditions. Acknowledgements: The study was funded by RFBR, according to the research project No. 16-34-60210 mol_а_dk, and by Russian Government Program of Competitive Growth of Kazan Federal University.


2016 ◽  
Vol 12 (1) ◽  
pp. 687-691 ◽  
Author(s):  
RAFFAELLA GIUFFRIDA ◽  
LUANA ADAMO ◽  
GIOACCHIN IANNOLO ◽  
LUISA VICARI ◽  
DARIO GIUFFRIDA ◽  
...  

2011 ◽  
Vol 129 (4) ◽  
pp. 820-831 ◽  
Author(s):  
Xiao-Qun Ye ◽  
Qi Li ◽  
Guang-Hui Wang ◽  
Fen-Fen Sun ◽  
Gui-Jun Huang ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9280
Author(s):  
Hilal Arnouk ◽  
Gloria Yum ◽  
Dean Shah

Cripto-1 is an essential protein for human development that plays a key role in the early phase of gastrulation in the differentiation of an embryo as well as assists with wound healing processes. Importantly, Cripto-1 induces epithelial to mesenchymal transition to turn fixed epithelial cells into a more mobile mesenchymal phenotype through the downregulation of epithelial adhesion molecules such as E-cadherin, occludins, and claudins, and the upregulation of mesenchymal, mobile proteins, such as N-cadherin, Snail, and Slug. Consequently, Cripto-1’s role in inducing EMT to promote cell motility is beneficial in embryogenesis, but detrimental in the formation, progression and metastasis of malignant tumors. Indeed, Cripto-1 is found to be upregulated in most cancers, such as breast, lung, gastrointestinal, hepatic, renal, cervical, ovarian, prostate, and skin cancers. Through its role in EMT, Cripto-1 can remodel cancer cells to enable them to travel through the extracellular matrix as well as blood and lymphatic vessels to metastasize to different organs. Additionally, Cripto-1 promotes the survival of cancer stem cells, which can lead to relapse in cancer patients.


2021 ◽  
Vol 43 (2) ◽  
pp. 1188-1202
Author(s):  
Saya Tamura ◽  
Takuma Hayashi ◽  
Hideki Tokunaga ◽  
Nobuo Yaegashi ◽  
Kaoru Abiko ◽  
...  

Uterine leiomyoma, also known as fibroids, is the most common benign neoplasm of the female genital tract. Leiomyoma is the most common uterine tumor. The leiomyoma subtypes account for approximately 10% of leiomyomas. Intravenous leiomyomatosis, a uterine leiomyoma subtype, is an intravascular growth of benign smooth muscle cells, occasionally with pelvic or extrapelvic extension. Uterine leiomyosarcoma, a malignant tumor, tends to metastasize hematogenously, and distant metastasis to the lungs and liver is common. Therefore, the oncological properties of this intravenous leiomyomatosis resemble those of the malignant tumor uterine leiomyosarcoma. Cancer stem cells migrate to distant organs via intravascular infiltration, leading to micrometastases. We examined the oncological properties of intravenous leiomyomatosis using molecular pathological techniques on tissue excised from patients with uterine leiomyoma. CD44-positive mesenchymal tumor stem-like cells were detected in both patients with intravenous leiomyomatosis and uterine leiomyosarcoma. The oncological properties of intravenous leiomyomatosis were found to be similar to those of uterine leiomyosarcoma. However, in intravenous leiomyomatosis, cyclin E and Ki-67-positive cells were rare and no pathological findings suspecting malignancy were observed. It is expected that establishing a treatment method targeting cancer stem cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.


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