Evidence for embryonic stem-like signature and epithelial-mesenchymal transition features in the spheroid cells derived from lung adenocarcinoma

Roudi, Raheleh; Madjd, Zahra; Ebrahimi, Marzieh; Najafi, Ali; Korourian, Alireza; Shariftabrizi, Ahmad; Samadikuchaksaraei, Alí

doi:10.1007/s13277-016-5041-y

Cited by 19 publications

(15 citation statements)

References 103 publications

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“…In addition, for lung cancer, there is no widespread consensus regarding the best CSC markers. 22 Consequently, "liquid biopsy" has been used for isolation and characterization of CSCs in almost all cancers as it has the potential to be used for frequent genetic analysis of tumor diagnosis/prognosis, in personalized therapy selection and provides considerable leverage of being detected at any tumor stage. [7][8][9]23 CTCs hold much more genetic/molecular information than free-circulating nucleic acid and proteins, thus revealing the importance of inter-cell heterogeneity in correlating cancer prognosis and treatment resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Roudi et al showed indicated loss of CD44 expression and gain of CD24 expression (CD44(−&x41;/CD24(+)) in spheroid cells obtained from A549 cell line. 22 However, these studies were based on tissue samples or cell line, while our study is based on the CTSCs isolated from the peripheral blood of NSCLC adenocarcinoma patients. Conversely, we have found CD44(+)/CD24(−) cells to be able to form larger spheres within a few days, indicative of their ability to undergo cell division due to enhanced self-renewal efficiency which could be perpetuated for many generations.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(−) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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“…Total RNA was extracted from MKN-45-miR-31 or the control groups using RNX-plus solution (Cat No. RN7713C, Cin-naGen Inc., Tehran, Iran) using the manufacturer's instructions (23). cDNA synthesis was performed using a kit for mRNA synthesis (Cat No.…”

Section: Rna Extraction Cdna Synthesis and Quantitative Rt-pcrmentioning

confidence: 99%

Induction of miR-31 causes increased sensitivity to 5-FU and decreased migration and cell invasion in gastric adenocarcinoma

Korourian¹,

Madjd²,

Roudi³

et al. 2019

BLL

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Drug resistance is the main obstacle in the treatment of gastric cancer, the third most common cause of cancer-related death in the world. Due to their small size, easy entrance to cells and multiple targets, microRNAs (miRs) are considered novel and attractive targets. In the current study, parental MKN-45, MKN-45-control vector, and MKN-45-miR-31 populations were compared in terms of cell cycle transitions, migration, cell invasion, and proliferation. In addition, downstream targets of miR-31, including E2F6, and SMUG1 were examined using Real-time RT-PCR and western blotting. MKN-45-miR-31 showed an increased sensitivity to 5-FU, decreased migration and cell invasion compared to the control groups (p = 0.0001, p = 0.01 and p = 0.01, respectively). There was a signifi cant increase in the percentage of cells in G1/pre-G1 phase in MKN-45-miR-31 relative to the control groups (p = 0.001). Induction of miR-31 expression in MKN-45 caused a signifi cant reduction of E2F6 and SMUG1 genes. Our fi ndings indicated that induction of miR-31 expression could increase drug sensitivity, and diminish tumor cell migration and invasion of gastric cancer cells. Therefore, miR-31 can be considered as a potential target molecule in the targeted therapy of gastric cancer (Fig. 2, Ref. 43).

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“…Approximately 7 × 10 5 of single viable cells were plated on poly-HEMA coated cell culture flasks in a serum-free medium. Fresh aliquots of EGF and bFGF were added every other day (21). Following culture for 10-12 days, SDCs were collected by gravity, washed with PBS, and detached with accutase (Sigma-Aldrich, USA), and they were then transferred into the cell culture coated flask to promote further generations.…”

Section: Cell Lines Culture and Sphere Formationmentioning

confidence: 99%

Spheroid-Derived Cells From Renal Adenocarcinoma Have Low Telomerase Activity and High Stem-Like and Invasive Characteristics

et al. 2019

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Cancer stem cells (CSCs) are a theorized small subpopulation of cells within tumors thought to be responsible for metastasis, tumor development, disease progression, treatment-resistance, and recurrence. The identification, isolation, and biological characterization of CSCs may therefore facilitate the development of efficient therapeutic strategies targeting CSCs. This study aims to compare the biology and telomerase activity of CSCs to parental cells (PCs) in renal cancer. Renal CSCs were enriched from the ACHN cell line using a sphere culture system. Spheroid-derived cells (SDCs) and their adherent counterparts were compared with respect to their colony and sphere formation, expression of putative CSC markers, tumorigenicity in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, and invasiveness. The expression of genes associated with CSCs, stemness, EMT, apoptosis, and ABC transporters was also compared between the two populations using quantitative real-time PCR (qRT-PCR). Finally, telomerase activity, hTERT expression, and sensitivity to MST-312, a telomerase inhibitor, was investigated between the two populations. We demonstrated that a subpopulation of ACHN cells was capable of growing as spheroids with many properties similar to CSCs, including higher clonogenicity, superior colony-and sphere-forming ability, and stronger tumorigenicity and invasiveness. In addition, SDCs demonstrated a higher expression of markers for CSCs, stemness, EMT, apoptosis, and ABC transporter genes compared to PCs. The expression of hTERT and telomerase activity in SDCs was significantly lower than PCs; however, the SDC population was more sensitive to MST-312 compared to PCs. These findings indicate that the SDC population exhibits stem-like potential and invasive characteristics. Moreover, the reduced expression of hTERT and telomerase activity in SDCs demonstrated that Saeednejad Zanjani et al. Telomerase Reduces in Renal CSCs the expressions of hTERT and telomerase activity are not always higher in CSCs. Our results also showed that MST-312 treatment inhibited SDCs more strongly than PCs and may therefore be useful as a complementary targeted therapy against renal CSCs in the future.

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Evidence for embryonic stem-like signature and epithelial-mesenchymal transition features in the spheroid cells derived from lung adenocarcinoma

Cited by 19 publications

References 103 publications

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Induction of miR-31 causes increased sensitivity to 5-FU and decreased migration and cell invasion in gastric adenocarcinoma

Spheroid-Derived Cells From Renal Adenocarcinoma Have Low Telomerase Activity and High Stem-Like and Invasive Characteristics

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