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

Raniszewska, Agata; Kwiecień, Iwona; Rutkowska, Elżbieta; Rzepecki, Piotr; Domagała‐Kulawik, Joanna

doi:10.3390/cancers13122996

Cited by 25 publications

(16 citation statements)

References 133 publications

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“…To date, CSCs have been identified in various solid tumor types including, but not limited to, brain, breast, colorectal, prostate and lung cancer (9)(10)(11)(12)(13). CSCs are frequently identified based on their expression of surface markers and several markers have been proposed for lung cancer, including CD44, CD90, CD133, CD166 and epithelial cell adhesion molecule (EPCAM) [reviewed in (14)].…”

Section: Introductionmentioning

confidence: 99%

Establishment of patient‑derived lung tumorspheres and their response to internal irradiation by Auger electrons

et al. 2022

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The high recurrence rate of lung cancer is a major clinical challenge associated with therapy-resistant cancer stem cells (CSCs), which are rare subpopulations. Future successful treatment is required to also eradicate these subpopulations. Furthermore, the majority of anti-cancer treatments are being tested in adherent monolayer cultures with the limitations this entails in the translation of results into clinical practice. The present study aimed to establish and characterize patient-derived long-term primary lung cancer tumorspheres enriched in CSCs and evaluate the effects of Auger electrons on them. These electrons are emitted from radionuclides that decay by electron capture or internal conversion and have demonstrated promising therapeutic potential. Their low energy (<1 keV) is sufficiently potent to induce DNA double-strand breaks and eventually cell death while minimizing irradiation of non-targeted surrounding cells. Labeling a thymidine analog (deoxyuridine) with the Auger electron-emitting radionuclide [ 125 I], which is exclusively incorporated into the DNA of proliferating cells during the S-phase, ensures a close distance to the DNA. Primary cell cultures grown as tumorspheres were established and characterized. The tumorspheres were morphologically distinct and differed concerning their proliferation rate and fraction of CSCs. Surface markers associated with CSCs were upregulated and 5-[ 125 I]iodo-2'-deoxyuridine was incorporated in the tumorspheres. The Auger electrons induced DNA double-strand breaks, G2/M arrest and apoptosis in the tumorspheres; however, the tumorspheres derived from different patients exhibited heterogeneities in their sensitivity to Auger electron irradiation.

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Section: Introductionmentioning

confidence: 99%

Establishment of patient‑derived lung tumorspheres and their response to internal irradiation by Auger electrons

et al. 2022

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“…Stem cell exhaustion, together with altered intercellular communications, represents the end result of other hallmarks of ageing and is ultimately responsible for the functional decline associated with ageing [2]. Molecular ageing of stem cells includes diminished homeostatic control, impaired stem cell response, senescence, apoptosis, aberrant differentiation, somatic mutations, altered functions and failed self-renewal (Figure 2) [51,52]. These changes are accompanied by altered expression of genes in ageing stem cells [53].…”

Section: Sox and Stemness-related Ageingmentioning

confidence: 99%

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

Stevanović

Lazic

Schwirtlich

et al. 2023

IJMS

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The quest for eternal youth and immortality is as old as humankind. Ageing is an inevitable physiological process accompanied by many functional declines that are driving factors for age-related diseases. Stem cell exhaustion is one of the major hallmarks of ageing. The SOX transcription factors play well-known roles in self-renewal and differentiation of both embryonic and adult stem cells. As a consequence of ageing, the repertoire of adult stem cells present in various organs steadily declines, and their dysfunction/death could lead to reduced regenerative potential and development of age-related diseases. Thus, restoring the function of aged stem cells, inducing their regenerative potential, and slowing down the ageing process are critical for improving the health span and, consequently, the lifespan of humans. Reprograming factors, including SOX family members, emerge as crucial players in rejuvenation. This review focuses on the roles of SOX transcription factors in stem cell exhaustion and age-related diseases, including neurodegenerative diseases, visual deterioration, chronic obstructive pulmonary disease, osteoporosis, and age-related cancers. A better understanding of the molecular mechanisms of ageing and the roles of SOX transcription factors in this process could open new avenues for developing novel strategies that will delay ageing and prevent age-related diseases.

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“…Accumulating evidence has demonstrated the existence of the small population of stem-like tumor cells in lung cancer is capable of multidirectional differentiation, self-renewal, unlimited proliferation, and efficient tumor formation in vivo [ 10 ]. The survival of these stem-like cells in targeted therapy, chemotherapy, radiotherapy, and immunotherapy is a leading cause of recurrence and drug resistance in lung cancer [ 11 ]. Although CSCs have been widely reported in various types of tumors, their mechanisms in lung cancer are still poorly understood [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

WDR72 Enhances the Stemness of Lung Cancer Cells by Activating the AKT/HIF-1α Signaling Pathway

Ouyang

Shi

Huang

et al. 2022

Journal of Oncology

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Objectives. Lung cancer is a common malignant tumor with high morbidity and mortality rate. Lung cancer stem cells are crucial in the development of lung cancer. In this study, we investigate WD repeat-containing protein 72 (WDR72) on lung cancer cell stemness and explore its underlying mechanism. Methods. WDR72 expression was investigated in lung cancer tissues and lung cancer stem cells by Western blot and RT-qPCR. The stemness of lung cancer stem cells was verified by the sphere-forming experiment and the abundance of stem cell markers. For the purpose of determining lung cancer stem cell growth, metastasis, and apoptosis, the CCK-8 assay, colony formation, Transwell migration, and flow cytometry were carried out. The ability of tumorigenesis in vivo was explored by xenograft tumor mouse models. Results. Up-regulation of WDR72 was found in lung cancer tissues and lung cancer stem cells. WDR72 overexpression significantly activated the AKT/HIF-1α signaling pathway. Application of PI3K/AKT pathway inhibitor LY29004 was able to counteract the impacts of WDR72 upregulation on genes related to stemness, growth, migration, and apoptosis in lung cancer stem cells. The sphere formation of lung cancer stem cells was significantly diminished after inhibiting the AKT/HIF-1α pathway. The promotion of WDR72 overexpression on lung cancer stem cell proliferation and metastasis was also eliminated by LY29004 treatment. Conclusion. WDR72 activates the AKT/HIF-1α signaling pathway to enhance the stemness of lung cancer stem cells and promote the growth and metastasis of lung cancer.

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

Cited by 25 publications

References 133 publications

Establishment of patient‑derived lung tumorspheres and their response to internal irradiation by Auger electrons

Establishment of patient‑derived lung tumorspheres and their response to internal irradiation by Auger electrons

The Role of SOX Transcription Factors in Ageing and Age-Related Diseases

WDR72 Enhances the Stemness of Lung Cancer Cells by Activating the AKT/HIF-1α Signaling Pathway

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