scholarly journals Lin28A Promotes the Amplification and Cancer Stemness of Lung Cancer Cells Via Activating MAPK Pathway Dependent on Let-7c Functions

2021 ◽  
Author(s):  
Rui Zhang ◽  
Pengpeng Liu ◽  
Xiao Zhang ◽  
Yingnan Ye ◽  
Jinpu Yu
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Culture System ◽  
3D Culture ◽  
Mapk Signaling ◽  
Cancer Stemness ◽  
Over Expression ◽  
3D Culture System

Abstract Background: Metastasis and relapse of lung cancer are the main cause of disease-related deaths. It’s reported that tumor metastasis and relapse originated from cancer stem cells (CSCs) which possess more potential in proliferation and invasion. In our previous studies, we established a conditional BME-based three-dimensional culture (3D culture) system to mimic the growth environment in vivo and further amplified lung cancer stem cells (LCSCs) in our system. However, the molecular mechanisms of the amplification and development of LCSCs in our 3D culture system are still not very clear. Methods: We tested the expression of Lin28 and let7 by western blot and qPCR, and constructed A549 cells either knockdown of Lin28 or overexpression of let7, followed by investigating the expression of stemness markers by flow cytometry and qPCR, and stem cell like phenotypes including cell proliferation, colony formation, mammosphere culture, cell apoptosis, migration, invasion and drug resistance in vitro, as well as tumorigenicity in vivo. Results: Here we observed Lin28A/let-7c was dysregulated in LCSCs both from the 3D culture system and from lung cancer tissues. Further, the abnormal expression of Lin28A/let-7c was correlated with poor survival outcomes. We found over-expression let-7c inhibited the maintenance of LCSC properties, while the results for knockdown of Lin28A showed Lin28A was critical for the enrichment and amplification of LCSCs via MAPK signaling pathway. Importantly, we found that either knockdown of Lin28A or over-expression of let-7c inhibited carcinogenesis and disrupted LCSC expansion in vivo. Conclusions: Our study uncovered the functions and mechanisms of the "Lin28A/let-7c/MAPK" signaling pathway in promoting the amplification and cancer stemness of LCSCs, which might be a potential therapeutic target for lung cancer therapy by reducing and even eliminating LCSCs in the future.

FGF1 and IGF1-conditioned 3D culture system promoted the amplification and cancer stemness of lung cancer cells

Biomaterials ◽  
2017 ◽  
Vol 149 ◽  
pp. 63-76 ◽  
Author(s):  
Pengpeng Liu ◽  
Rui Zhang ◽  
Wenwen Yu ◽  
Yingnan Ye ◽  
Yanan Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Culture System ◽  
3D Culture ◽  
Lung Cancer Cells ◽  
Cancer Stemness ◽  
3D Culture System

scholarly journals Mixed enzymatic-explant protocol for isolation of mesenchymal stem cells from Wharton’s jelly and encapsulation in 3D culture system

2012 ◽  
Vol 05 (10) ◽  
pp. 580-586 ◽  
Author(s):  
Saeed Azandeh ◽  
Mahmoud Orazizadeh ◽  
Mahmoud Hashemitabar ◽  
Ali Khodadadi ◽  
Ali Akbar Shayesteh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture System ◽  
3D Culture ◽  
Wharton’S Jelly ◽  
Wharton's Jelly ◽  
3D Culture System

scholarly journals ID: 1023 All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth

2017 ◽  
Vol 4 (S) ◽  
pp. 98
Author(s):  
P H Nguyen ◽  
J Giraud ◽  
C Staedel ◽  
L Chambonnier ◽  
P Dubus ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Gastric Carcinoma ◽  
Tumor Growth ◽  
Cell Cycle Progression ◽  
3D Culture ◽  
All Trans Retinoic Acid

Gastric carcinoma is the third leading cause of cancer-related death worldwide. This cancer, most of the time metastatic, is essentially treated by surgery associated with conventional chemotherapy, and has a poor prognosis. The existence of cancer stem cells (CSC) expressing CD44 and a high aldehyde dehydrogenase (ALDH) activity has recently been demonstrated in gastric carcinoma and has opened new perspectives to develop targeted therapy. In this study, we evaluated the effects of all-transretinoic acid (ATRA) on CSCs in human gastric carcinoma. ATRA effects were evaluated on the proliferation and tumorigenic properties of gastric carcinoma cells from patient-derived tumors and cell lines in conventional 2D cultures, in 3D culture systems (tumorsphere assay) and in mouse xenograft models. ATRA inhibited both tumorspheres initiation and growth in vitro, which was associated with a cell-cycle arrest through the upregulation of cyclin-dependent kinase (CDK) inhibitors and the downregulation of cell-cycle progression activators. More importantly, ATRA downregulated the expression of the CSC markers CD44 and ALDH as well as stemness genes such as Klf4 and Sox2 and induced differentiation of tumorspheres. Finally, 2 weeks of daily ATRA treatment were sufficient to inhibit gastric tumor progression in vivo, which was associated with a decrease in CD44, ALDH1, Ki67 and PCNA expression in the remaining tumor cells. Administration of ATRA appears to be a potent strategy to efficiently inhibit tumor growth and more importantly to target gastric CSCs in both intestinal and diffuse types of gastric carcinoma.

Regeneration of insulin-producing islets from dental pulp stem cells using a 3D culture system

2018 ◽  
Vol 13 (6) ◽  
pp. 673-687 ◽  
Author(s):  
Hiromi Yagi Mendoza ◽  
Tomomi Yokoyama ◽  
Tomoko Tanaka ◽  
Hisataka Ii ◽  
Ken Yaegaki
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Culture System ◽  
3D Culture ◽  
Dental Pulp Stem Cells ◽  
3D Culture System

scholarly journals Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

2018 ◽  
Vol 47 (5) ◽  
pp. 2109-2125 ◽  
Author(s):  
Zhaocong Yang ◽  
Yanfeng Zhang ◽  
Tingting Tang ◽  
Qinhua Zhu ◽  
Wanyue Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Culture System ◽  
High Throughput Sequencing ◽  
Semi Solid ◽  
Pancreatic Cancer Stem Cells ◽  
Solid System

Background/Aims: Pancreatic cancer remains one of the deadliest human malignancies, the lethality of which may be attributed to the presence of pancreatic cancer stem cells (PCSCs), a small subpopulation of cells existing within pancreatic tumor with high carcinogenesis. Therefore, it is crucial to establish an efficient enrichment and culture system of PCSCs and identify the key genes involved in the regulation of PCSCs. The three-dimensional (3D) liquid suspension mammosphere culture system has been established for enrichment and culture of PCSCs in vitro as the cell spheres are likely to originate from individual cell clone, but it has been challenged because the cell spheroids could be a result of cell aggregation. Methods: We optimized the existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented the non-specific aggregation. Then we identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. Subsequently, we performed high-throughput sequencing (HTS) of the Panc-1 spheroid cells. Results: We confirmed the PCSCs properties and high malignancy of the Panc-1 spheroid cells enriched by our novel 3D semi-solid system both in vitro and in vivo. Hundreds of mRNA, microRNA (miRNA) and dozens of long non-coding RNA (LncRNA) were identified to be differentially regulated in PCSCs-like Panc-1 spheroid cells compared with their parental cells by HTS. Conclusions: Our results demonstrate an efficient enrichment and culture system for Panc-1 spheroid cells with the PCSCs properties. The differentially expressed genes and their targets identified by the HTS of the Panc-1 spheroid cells can serve as new potential biomarkers for pancreatic cancer diagnosis and targeted therapy.

scholarly journals A macrophage and theca cell-enriched stromal cell population influences growth and survival of immature murine follicles in vitro

Reproduction ◽  
2011 ◽  
Vol 141 (6) ◽  
pp. 809-820 ◽  
Author(s):  
Candace M Tingen ◽  
Sarah E Kiesewetter ◽  
Jennifer Jozefik ◽  
Cristina Thomas ◽  
David Tagler ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Culture System ◽  
Stromal Cell ◽  
Ovarian Follicle ◽  
3D Culture ◽  
Culture Conditions ◽  
Growth And Survival ◽  
3D Culture System

Innovations in in vitro ovarian follicle culture have revolutionized the field of fertility preservation, but the successful culturing of isolated primary and small secondary follicles remains difficult. Herein, we describe a revised 3D culture system that uses a feeder layer of ovarian stromal cells to support early follicle development. This culture system allows significantly improved primary and early secondary follicle growth and survival. The stromal cells, consisting mostly of thecal cells and ovarian macrophages, recapitulate the in vivo conditions of these small follicles and increase the production of androgens and cytokines missing from stromal cell-free culture conditions. These results demonstrate that small follicles have a stage-specific reliance on the ovarian environment, and that growth and survival can be improved in vitro through a milieu created by pre-pubertal ovarian stromal cell co-culture.

Collagen-alginate microspheres as a 3D culture system for mouse embryonic stem cells differentiation to primordial germ cells

Biologicals ◽  
2017 ◽  
Vol 48 ◽  
pp. 114-120 ◽  
Author(s):  
Vahid Mansouri ◽  
Mohammad Salehi ◽  
Mir davood Omrani ◽  
Zahra Niknam ◽  
Abdolreza Ardeshirylajimi
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cells ◽  
Culture System ◽  
Primordial Germ Cells ◽  
Embryonic Stem ◽  
3D Culture ◽  
Mouse Embryonic Stem Cells ◽  
3D Culture System

scholarly journals Combination of Sasa quelpaertensis Nakai Leaf Extract and Cisplatin Suppresses the Cancer Stemness and Invasion of Human Lung Cancer Cells

2014 ◽  
Vol 13 (6) ◽  
pp. 529-540 ◽  
Author(s):  
Mina Kim ◽  
Yoo-Sun Kim ◽  
Kyung-Mi Kim ◽  
Hee-Chul Ko ◽  
Se-Jae Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Human Lung ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Stem Cell Markers ◽  
Cancer Stemness ◽  
Human Lung Cancer Cells

Lung cancer is the leading cause of cancer death worldwide, and most chemotherapeutic drugs have limited success in treating this disease. Furthermore, some drugs show undesirable side effects due to the enrichment of cancer stem cells (CSCs) that are present, leading to resistance to conventional chemotherapy and tumor relapse. CSCs possess self-renewal characteristics, aggressive tumor initiating activity, and ability to facilitate tumor metastasis. Therefore, development of nontoxic agents that can potentiate chemotherapy and eliminate CSCs would be highly desirable. In the present study, we investigated whether Sasa quelpaertensis leaf extracts (SQE) and cisplatin (CIS), individually or in combination, would exert anti-CSC and antimetastatic effect in H1299 and A549 human lung cancer cells. Following these treatments, cell growth, phosphorylation of phosphoinositide-3 kinase, and activation of the mammalian target of rapamycin were inhibited. Decreased serial sphere formation, clonogenicity, and expression of major stem cell markers, such as CD44 and SOX-2, in CD44+ cancer stem cells were also observed. In addition, inhibition of cell migration and invasion in both cell lines as well as inhibition of matrix metalloproteinase-2 activity and expression were detected. Importantly, the anticancer stemness and antimetastasis effects in each of these assays were greater for the combined treatment with SQE and CIS than with each treatment individually. In conclusion, the data suggest that SQE alone, or in combination with CIS, represents a promising therapeutic strategy for eliminating cancer stemness and cell invasion potential of CSCs, thereby treating and preventing metastatic lung cancer cells.

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