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 ◽  
...  
2021 ◽  
Author(s):  
Rui Zhang ◽  
Pengpeng Liu ◽  
Xiao Zhang ◽  
Yingnan Ye ◽  
Jinpu Yu

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.


2014 ◽  
Vol 13 (6) ◽  
pp. 529-540 ◽  
Author(s):  
Mina Kim ◽  
Yoo-Sun Kim ◽  
Kyung-Mi Kim ◽  
Hee-Chul Ko ◽  
Se-Jae Kim ◽  
...  

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.


Pathobiology ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 291-301 ◽  
Author(s):  
Shoko Murakami ◽  
Ken-ichi Mukaisho ◽  
Takuya Iwasa ◽  
Masaaki Kawabe ◽  
Saori Yoshida ◽  
...  

<b><i>Background:</i></b> We developed a 3-dimensional (3D) culture system using a high-purity silica fiber scaffold of unwoven sheets called Cellbed<sup>TM</sup>. <b><i>Methods:</i></b> We used adherent colon and esophagogastric junction adenocarcinoma cells, tongue squamous cell carcinoma (SqCC) cells, and nonadherent gastric cancer cells. These cells were subjected to staining with various substances and observed by electron microscopy. To evaluate the effects of extracellular matrix in carcinoma tissues, SqCC cells were cultured in Cellbed coated with collagens I, III, and IV. <b><i>Results:</i></b> Especially well-differentiated carcinoma cells cultured in this 3D system showed their own unique characteristics: luminal formation in adenocarcinoma cells and cell stratification and keratinization in SqCC cells. Scanning electron microscopy revealed the proliferation of cancer cells with cytoplasm entwined in Cellbed. Intercellular desmosomes in squamous epithelia were detected by transmission electron microscopy of vertical cross sections. SqCC cells cultured in Cellbed coated with collagen IV showed enhanced invasive and proliferative abilities. <b><i>Conclusion:</i></b> Because the morphology of cancer cells cultured in this 3D culture system is similar to that in living organisms, we called the system a “tissueoid cell culture system.” Coating with collagen IV enables the modification of cell-matrix interactions as well as recapitulation of the in vivo microenvironment.


2016 ◽  
Vol 11 (1) ◽  
pp. 24-25 ◽  
Author(s):  
Pithi Chanvorachote ◽  
Varisa Pongrakhananon ◽  
Chatchai Chaotham

2021 ◽  
Vol 4 (s1) ◽  
Author(s):  
Désirée Baruffaldi ◽  
Marta Canta ◽  
Candido Fabrizio Pirri ◽  
Francesca Frascella

A 3D culture system based on a photocurable matrix has been developed. The aim is to create a 3D printable platform mimicking lung cancer tissue, to study tumor microenvironment evolution, in terms of structural (architecture) and molecular (signalling) components.


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