Research progress on lung cancer stem cells in epidermal growth factor receptor–tyrosine kinase inhibitor targeted therapy resistance in lung adenocarcinoma

Lung cancer is the leading cause of cancer-related deaths globally.In recent years,with the widespread use of genetic testing,epidermal growth factor receptor–tyrosine kinase inhibitor(EGFR-TKI)–targeted drugs have been efficacious to patients with lung adenocarcinoma exhibiting EGFR mutations.However,resistance to treatment is inevitable and eventually leads to tumor progression,recurrence,and reduction in the overall treatment efficacy.Lung cancer stem cells play a crucial role in the development of resistance toward EGFR-TKI–targeted therapy for lung adenocarcinoma.Lung cancer stem cells possess self-renewal,multilineage differentiation,and unlimited proliferation capabilities,which efficiently contribute to tumor formation and ultimately lead to tumor recurrence andmetastasis.In this study,we evaluated the origin,markers,stemness index,relevant classic studies,resistance mechanisms,related signaling pathways,and strategies for reversing lung cancer stem cell resistance to EGFR-TKIs to provide new insights on delaying or reducing resistance and to improve the treatment efficacy of patients with EGFR-mutated lung adenocarcinoma in the future.

Lung stem cells in regeneration and tumorigenesis

Adult lung is a highly quiescent organ,with extremely low cell turnover frequency.However,emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries.Lung regeneration mainly depends on the proliferation of regionally distributed pulmonary stem cells that re-enter the cell cycle.Genetic lineage-tracing approaches help to track the lung epithelial differentiation and/or de-differentiation path,and single-cell transcriptomic technique reveals the essential molecular signaling involved in lung regeneration.Dysregulation of the molecular signaling that balances quiescence and self-renewal leads to the transformation of lung stem cells,and thus promotes lung cancer development.Interestingly,different subtypes of lung cancer share common cells of origin and the pathological transition among various subtypes is responsible for drug resistance in the clinic.In this review,we summarize the recent understanding of lung stem cells in regeneration and tumorigenesis as well as related molecular mechanisms,with the hope to provide helpful insights for clinical treatments of respiratory diseases.

Embryonic stem cells against non-small cell lung cancer in vivo

Objective To investigate the function and mechanism of embryonic stem cells again Lewis non-small cell lung cancer in vivo. Methods Based on the mouse Lewis non-small cell lung cancer model,we have tested some tumor growth indexes and investigated the immune response of embryonic stem cells against cancer cells. Results Compared with the mice in control group,mice

Interaction between LCSCs and lung cancer microenvironment and TCM intervention

Lung cancer has become a leading cause of cancer-related death because of its high morbidity and mortality.Although some progress has been made in the diagnosis,surgery,chemoradiotherapy,and other aspects of lung cancer in the last decade,actually there is no substantial breakthrough for the 5-year survival rate of patients has no significant improvement and is still below 15%.Plenty of evidence suggests that malignant tumors including lung cancer have a unique subgroup of cells featured with self-renewal and multidirectional differentiation potential.Cancer stem cells(CSCs)are the root of tumor growth and metastasis,and the characteristic changes of malignant phenotype(such as recurrence,invasion and metastasis,and drug resistance)are closely linked with CSCs.This paper explored the possible correlated mechanism of the complex interaction between lung cancer stem cells(LCSCs)and lung cancer microenvironment,to provide ideas for the R&D of relevant treatment technologies,the promotion of the progress in traditional medical technology,and the breakthrough of the bottleneck of long-term effect of lung cancer.

The diversity of adult lung epithelial stem cells and their niche in homeostasis and regeneration

The adult lung,a workhorse for gas exchange,is continually subjected to a barrage of assaults from the inhaled particles and pathogens.Hence,homeostatic maintenance is of paramount importance.Epithelial stem cells interact with their particular niche in the adult lung to orchestrate both natural tissue rejuvenation and robust post-injury regeneration.Advances in single-cell sequencing,lineage tracing,and living tissue imaging have deepened our understanding about stem cell heterogeneities,transition states,and specific cell lineage markers.In this review,we provided an overview of the known stem/progenitor cells and their subpopulations in different regions of the adult lung,and explored the regulatory networks in stem cells and their respective niche which collectively coordinated stem cell quiescence and regeneration states.We finally discussed relationships between dysregulated stem cell function and lung disease.

Intravenous transplantation of mesenchymal stem cells attenuates oleic acid induced acute lung injury in rats

Background Acute lung injury （ALl） and end-stage acute respiratory distress syndrome （ARDS） were among the most common causes of death in intensive care units. The activation of an inflammatory response and the damage of pulmonary epithelium and endotheliumwerethe hallmark of ALI/ARDS. Recent studies had demonstrated the importance of mesenchymal stem cells （MSCs） in maintaining the normal pulmonary endothelial and epithelial function as well as participating in modulating the inflammatory response and they are involved in epithelial and endothelial repair after injury. Here, our study demonstrates MSCs therapeutic potential in a rat model of ALI/ARDS. Methods Bone marrow derived MSCs were obtained from Sprague-Dawley （SD） rats and their differential potential was verified. ALl was induced in rats byoleic acid （OA）, and MSCs were transplanted intravenously. The lung injury and the concentration of cytokines in plasma and lung tissue extracts were assessed at 8 hours, 24 hours and 48 hours after OA-injection. Results The histological appearance and water content in rat lung tissue were significantly improved at different time points in rats treated with MSCs. The concentration of tumor necrosis factor-a and intercellular adhesion molecular-1 in rats plasma and lung tissue extracts were significantly inhibited after intravenous transplantation of MSCs, whereas interleukin-10 was significantly higher after MSCs transplantation at 8 hours, 24 hours and 48 hours after OA-challenge. Conclusions Intravenous transplantation of MSCs could maintain the integrity of the pulmonary alveolar-capillary barrier and modulate the inflammatory response to attenuate the experimental ALI/ARDS. Transplantation of MSCs could be a novel cell-based therapeutic strategy for prevention and treatment of ALI/ARDS.