scholarly journals Impact of Cancer Stem Cells and Cancer Stem Cell-Driven Drug Resiliency in Lung Tumor: Options in Sight

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 267
Author(s):  
Lourdes Cortes-Dericks ◽  
Domenico Galetta
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Lung Tumor ◽  
Current Knowledge ◽  
Immune Surveillance ◽  
Treatment Strategies ◽  
Resistant Cell ◽  
New Treatment ◽  
Efficient Elimination

Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.

scholarly journals Lung Cancer Stem Cells

2008 ◽  
Vol 24 (4-5) ◽  
pp. 257-266 ◽  
Author(s):  
Sharon R. Pine ◽  
Blair Marshall ◽  
Lyuba Varticovski
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cell Signaling ◽  
Current Knowledge ◽  
Lung Cancer Stem Cells ◽  
Multipotent Differentiation ◽  
Cancer Types ◽  
Active Research

Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

scholarly journals New Treatment Strategies to Eradicate Cancer Stem Cells and Niches in Glioblastoma

2013 ◽  
Vol 53 (11) ◽  
pp. 764-772 ◽  
Author(s):  
Takuichiro HIDE ◽  
Keishi MAKINO ◽  
Hideo NAKAMURA ◽  
Shigetoshi YANO ◽  
Shigeo ANAI ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
New Treatment

scholarly journals Gigantol Targets Cancer Stem Cells and Destabilizes Tumors via the Suppression of the PI3K/AKT and JAK/STAT Pathways in Ectopic Lung Cancer Xenografts

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2032 ◽  
Author(s):  
Nattanan Losuwannarak ◽  
Arnatchai Maiuthed ◽  
Nakarin Kitkumthorn ◽  
Asada Leelahavanichkul ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Treatment Strategies ◽  
Tumor Initiation ◽  
Mice Model ◽  
Ki 67 ◽  
Targeting Therapy

Lung cancer has long been recognized as an important world heath concern due to its high incidence and death rate. The failure of treatment strategies, as well as the regrowth of the disease driven by cancer stem cells (CSCs) residing in the tumor, lead to the urgent need for a novel CSC-targeting therapy. Here, we utilized proteome alteration analysis and ectopic tumor xenografts to gain insight on how gigantol, a bibenzyl compound from orchid species, could attenuate CSCs and reduce tumor integrity. The proteomics revealed that gigantol affected several functional proteins influencing the properties of CSCs, especially cell proliferation and survival. Importantly, the PI3K/AKT/mTOR and JAK/STAT related pathways were found to be suppressed by gigantol, while the JNK signal was enhanced. The in vivo nude mice model confirmed that pretreatment of the cells with gigantol prior to a tumor becoming established could decrease the cell division and tumor maintenance. The results indicated that gigantol decreased the relative tumor weight with dramatically reduced tumor cell proliferation, as indicated by Ki-67 labeling. Although gigantol only slightly altered the epithelial-to-mesenchymal and angiogenesis statuses, the gigantol-treated group showed a dramatic loss of tumor integrity as compared with the well-grown tumor mass of the untreated control. This study reveals the effects of gigantol on tumor initiation, growth, and maintain in the scope that the cells at the first step of tumor initiation have lesser CSC property than the control untreated cells. This study reveals novel insights into the anti-tumor mechanisms of gigantol focused on CSC targeting and destabilizing tumor integrity via suppression of the PI3K/AKT/mTOR and JAK/STAT pathways. This data supports the potential of gigantol to be further developed as a drug for lung cancer.

scholarly journals Breast Cancer Stem Cells

Biomedicines ◽  
2018 ◽  
Vol 6 (3) ◽  
pp. 77 ◽  
Author(s):  
Judy Crabtree ◽  
Lucio Miele
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Tumor Heterogeneity ◽  
Treatment Strategies ◽  
Clinical Development ◽  
Developmental Pathways ◽  
Breast Cancer Stem Cells ◽  
Cell Surface Markers ◽  
New Treatment

Breast cancer stem cells (BCSC) have been implicated in tumor initiation, progression, metastasis, recurrence, and resistance to therapy. The origins of BCSCs remain controversial due to tumor heterogeneity and the presence of such small side populations for study, but nonetheless, cell surface markers and their correlation with BCSC functionality continue to be identified. BCSCs are driven by persistent activation of developmental pathways, such as Notch, Wnt, Hippo, and Hedgehog and new treatment strategies that are aimed at these pathways are in preclinical and clinical development.

scholarly journals The Role and Molecular Mechanism of SLC34A2 in Stemness Maintenance of CD44+CD166+ Lung Cancer Stem Cells (LCSCs) with AT-II cells’ characteristics

2021 ◽  
Author(s):  
Yan Yang ◽  
Qiang Pu ◽  
Hu Liao ◽  
Yue Yuan ◽  
Xueting Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Malignant Transformation ◽  
Lung Tumor ◽  
Alveolar Epithelium ◽  
Migration And Invasion ◽  
Lung Cancer Stem Cells

Abstract Background Evidence showed some non-small cell lung cancers (NSCLCs) had the type II alveolar epithelium cells’(AT-II cells) characteristics, and AT-II cells were a kind of original stem cells of NSCLCs. But how AT-II cells malignantly transformed into NSCLCs was unclear. Recent evidence indicated SLC34A2 was critical in the development of AT-II cells, and SLC34A2 might be a new gene in the initiation of NSCLCs. However, whether SLC34A2 participated in the malignant transformation of AT-II cells remained unknown. The exact role and mechanism of SLC34A2 in the initiation of NSCLCs needed to be further investigated. Methods The expression of Napi-IIb (encoded by SLC34A2) in the NSCLC cells was compared with that in AT-II cells using immunohistochemistry (IHC). Also coexpression of CD44 and CD166 was detected in these NSCLCs tissues by IHC. Then the CD44+CD166+ cells were sorted from lung tumor spheres by FACS. They were assessed by sphere, proliferation and tumorgenicity assay. Besides, their expression of surfactants C(SP-C) was stained by IHC. Next, the role and mechanism of SLC34A2 in CD44+CD166+ lung cancer stem cells were explored by siRNA-mediated SLC34A2 knockdown, related pathway pharmacological inhibition or activation. In vitro findings were furtherly validated in vivo and NSCLCs samples. Results The expression of SLC34A2 was downregulated in NSCLCs cells compared with AT-II cells in clinic samples. Then the CD44+CD166+ population was identified as CD44+CD166+ lung cancer stem cells (LCSCs). And LCSCs showed abundant expression of SP-C, the hallmark of AT-II cells. Higher expression of SLC34A2 was found in LCSCs compared to their origin NSCLC cells. Additionally, the expression of SLC34A2 was decreased after LCSCs were differentiated, and the morphology of the differentiated cells from LCSCs was similar to their origin NSCLC cells. Knockdown SLC34A2 made declined abilities of self-renewal, drug-resistance, migration and invasion in vitro as well as tumorigenicity in vivo in LCSCs. And SLC34A2 could maintain stemness of LCSCs via PI3K/AKT/STAT3/Sox2 axis. Besides, the connection between SLC34A2 maintaining stemness of lung cancer stem cells and PI3K/AKT/STAT3/Sox2 axis was also validated in vivo and in clinic samples. Conclusions For the first time, we illustrated the expression of SLC34A2 was downregulated in NSCLCs cells compared with AT-II cells. We discovered the downregulated expression of SLC34A2 performed a vital role in the malignant transformation of AT-II cells into NSCLCs. And SLC34A2 could maintain stemness of CD44+CD166+ lung cancer stem cells, which were with AT-II cell’s characteristic, via PI3K/AKT/STAT3/Sox2 axis. It had important significance in the revelation of a new mechanism for the initiation of NSCLCs.

scholarly journals Targeting multiple genes containing long mononucleotide A-T repeats in lung cancer stem cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Narumol Bhummaphan ◽  
Piyapat Pin-on ◽  
Preeyaporn Plaimee Phiboonchaiyanan ◽  
Jirattha Siriluksana ◽  
Chatchawit Aporntewan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cell ◽  
Transcriptional Control ◽  
Single Gene ◽  
Repeat Sequence ◽  
Control Activity ◽  
Multiple Genes ◽  
Lung Cancer Stem Cells

Abstract Background Intratumour heterogeneous gene expression among cancer and cancer stem cells (CSCs) can cause failure of current targeted therapies because each drug aims to target the function of a single gene. Long mononucleotide A-T repeats are cis-regulatory transcriptional elements that control many genes, increasing the expression of numerous genes in various cancers, including lung cancer. Therefore, targeting A-T repeats may dysregulate many genes driving cancer development. Here, we tested a peptide nucleic acid (PNA) oligo containing a long A-repeat sequence [A(15)] to disrupt the transcriptional control of the A-T repeat in lung cancer and CSCs. Methods First, we separated CSCs from parental lung cancer cell lines. Then, we evaluated the role of A-T repeat gene regulation by counting the number of repeats in differentially regulated genes between CSCs and the parental cells of the CSCs. After testing the dosage and effect of PNA-A15 on normal and cancer cell toxicity and CSC phenotypes, we analysed genome-wide expression to identify dysregulated genes in CSCs. Results The number of A-T repeats in genes differentially regulated between CSCs and parental cells differed. PNA-A15 was toxic to lung cancer cells and CSCs but not to noncancer cells. Finally, PNA-A15 dysregulated a number of genes in lung CSCs. Conclusion PNA-A15 is a promising novel targeted therapy agent that targets the transcriptional control activity of multiple genes in lung CSCs.

scholarly journals “Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

2021 ◽  
Vol 22 (4) ◽  
pp. 1824
Author(s):  
Matthias Mietsch ◽  
Rabea Hinkel
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Treatment Strategies ◽  
Cardiac Cells ◽  
Aging Effects ◽  
Beneficial Effects ◽  
Micro Rnas ◽  
New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

scholarly journals Lung Cancer Stem Cells—Origin, Diagnostic Techniques and Perspective for Therapies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2996
Author(s):  
Agata Raniszewska ◽  
Iwona Kwiecień ◽  
Elżbieta Rutkowska ◽  
Piotr Rzepecki ◽  
Joanna Domagała-Kulawik
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Early Recognition ◽  
Human Life ◽  
Clonal Evolution ◽  
Diagnostic Techniques ◽  
Complex Processes ◽  
Age Related ◽  
Lung Cancer Stem Cells

Lung cancer remains one of the most aggressive solid tumors with an overall poor prognosis. Molecular studies carried out on lung tumors during treatment have shown the phenomenon of clonal evolution, thereby promoting the occurrence of a temporal heterogeneity of the tumor. Therefore, the biology of lung cancer is interesting. Cancer stem cells (CSCs) are involved in tumor initiation and metastasis. Aging is still the most important risk factor for lung cancer development. Spontaneously occurring mutations accumulate in normal stem cells or/and progenitor cells by human life resulting in the formation of CSCs. Deepening knowledge of these complex processes and improving early recognition and markers of predictive value are of utmost importance. In this paper, we discuss the CSC hypothesis with an emphasis on age-related changes that initiate carcinogenesis. We analyze the current literature in the field, describe our own experience in CSC investigation and discuss the technical challenges with special emphasis on liquid biopsy.

scholarly journals Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianyu Wang ◽  
Doudou Liu ◽  
Zhiwei Sun ◽  
Ting Ye ◽  
Jingyuan Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Lines ◽  
Human Cancer ◽  
Suppressor Activity ◽  
Self Renewal ◽  
Tumor Suppressor Activity ◽  
Lung Cancer Stem Cells ◽  
First Time

AbstractIt has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

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