scholarly journals Proximity proteomics identifies cancer cell membrane cis-molecular complex as a potential cancer target

2018 ◽  
Author(s):  
Norihiro Kotani ◽  
Arisa Yamaguchi ◽  
Tomoko Ohnishi ◽  
Ryusuke Kuwahara ◽  
Takanari Nakano ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Primary Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Multiple Drug ◽  
Cancer Treatments ◽  
Lung Cancer Patients

ABSTRACTCancer-specific antigens expressed in the cell membrane have been used as targets for several molecular targeted strategies in recent years with remarkable success. To develop more effective cancer treatments, novel targets and strategies for targeted therapies are needed. Here, we examined the cancer cell membrane-resident “cis-bimolecular complex” as a possible cancer target (cis-bimolecular cancer target: BiCAT) using proximity proteomics, a technique that has attracted attention in recent years. BiCATs were detected using a previously developed method, termed the enzyme-mediated activation of radical source (EMARS), to label the components proximal to a given cell membrane molecule. EMARS analysis identified some BiCATs, such as close homolog of L1 (CHL1), fibroblast growth factor 3 (FGFR3) and α2 integrin, which are commonly expressed in mouse primary lung cancer cells and human lung squamous cell carcinoma cells. Analysis of cancer specimens from 55 lung cancer patients revealed that approximately half of patients were positive for these BiCATs. In vitro simulation of effective drug combinations used for multiple drug treatment strategy was performed using reagents targeted to BiCAT molecules. The combination treatment based on BiCAT information moderately suppressed cancer cell proliferation compared with single administration, suggesting that the information about BiCATs in cancer cells is profitable for the appropriate selection of the combination among molecular targeted reagents. Thus, BiCAT has the possibility to make a contribution to several molecular targeted strategies in future.

scholarly journals Cancer Cell Membrane Decorated Silica Nanoparticle Loaded with miR495 and Doxorubicin to Overcome Drug Resistance for Effective Lung Cancer Therapy

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jinyuan He ◽  
Chulian Gong ◽  
Jie Qin ◽  
Mingan Li ◽  
Shaohong Huang
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Silica Nanoparticle ◽  
Glycoprotein P ◽  
Lung Cancer Therapy

Abstract Current cancer therapy usually succumbs to many extracellular and intracellular barriers, among which untargeted distribution and multidrug resistance (MDR) are two important difficulties responsible for poor outcome of many drug delivery systems (DDS). Here, in our study, the dilemma was addressed by developing a cancer cell membrane (CCM)-coated silica (SLI) nanoparticles to co-deliver miR495 with doxorubicin (DOX) for effective therapy of lung cancer (CCM/SLI/R-D). The homologous CCM from MDR lung cancer cells (A549/DOX) was supposed to increase the tumor-homing property of the DDS to bypass the extracellular barriers. Moreover, the MDR of cancer cells were conquered through downregulation of P-glycoprotein (P-gp) expression using miR495. It was proved that miR495 could significantly decrease the expression of P-gp which elevated intracellular drug accumulation in A549/DOX. The in vitro and in vivo results exhibited that CCM/SLI/R-D showed a greatly enhanced therapeutic effect on A549/DOX, which was superior than applying miR495 or DOX alone. The preferable effect of CCM/SLI/R-D on conquering the MDR in lung cancer provides a novel alternative for effective chemotherapy of MDR cancers.

scholarly journals Circular RNA FLNA acts as a sponge of miR-486-3p in promoting lung cancer progression via regulating XRCC1 and CYP1A1

2021 ◽  
Author(s):  
Jiongwei Pan ◽  
Gang Huang ◽  
Zhangyong Yin ◽  
Xiaoping Cai ◽  
Enhui Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Lung Cancer Cells ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Related Factors

AbstractSignificantly high-expressed circFLNA has been found in various cancer cell lines, but not in lung cancer. Therefore, this study aimed to explore the role of circFLNA in the progression of lung cancer. The target gene of circFLNA was determined by bioinformatics and luciferase reporter assay. Viability, proliferation, migration, and invasion of the transfected cells were detected by CCK-8, colony formation, wound-healing, and transwell assays, respectively. A mouse subcutaneous xenotransplanted tumor model was established, and the expressions of circFLNA, miR-486-3p, XRCC1, CYP1A1, and related genes in the cancer cells and tissues were detected by RT-qPCR, Western blot, or immunohistochemistry. The current study found that miR-486-3p was low-expressed in lung cancer. MiR-486-3p, which has been found to target XRCC1 and CYP1A1, was regulated by circFLNA. CircFLNA was located in the cytoplasm and had a high expression in lung cancer cells. Cancer cell viability, proliferation, migration, and invasion were promoted by overexpressed circFLNA, XRCC1, and CYP1A1 but inhibited by miR-486-3p mimic and circFLNA knockdown. The weight of the xenotransplanted tumor was increased by circFLNA overexpression yet reduced by miR-486-3p mimic. Furthermore, miR-486-3p mimic reversed the effect of circFLNA overexpression on promoting lung cancer cells and tumors and regulating the expressions of miR-486-3p, XRCC1, CYP1A1, and metastasis/apoptosis/proliferation-related factors. However, overexpressed XRCC1 and CYP1A1 reversed the inhibitory effect of miR-486-3p mimic on cancer cells and tumors. In conclusion, circFLNA acted as a sponge of miR-486-3p to promote the proliferation, migration, and invasion of lung cancer cells in vitro and in vivo by regulating XRCC1 and CYP1A1.

scholarly journals Tumor-Intrinsic Response to IFNγ Shapes the Tumor Microenvironment and Anti-PD-1 Response in NSCLC

2019 ◽  
Author(s):  
Bonnie L. Bullock ◽  
Abigail K. Kimball ◽  
Joanna M. Poczobutt ◽  
Howard Y. Li ◽  
Jeff W. Kwak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Rna Seq ◽  
Lung Cancer Cell ◽  
Immunocompetent Mouse ◽  
Lung Cancer Patients ◽  
T Cell Infiltration ◽  
Basal Expression

AbstractTargeting PD-1/ PD-L1 is only effective in ~20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras lung cancer cell lines to anti-PD-1 therapy: CMT167 tumors were eliminated while LLC tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference. RNA-Seq analysis of cancer cells recovered from lung tumors revealed that CMT167 cells induced an IFNγ signature that was absent in LLC cells. Silencing Ifngr1 in CMT167 resulted in tumors resistant to IFNγ and anti-PD-1 therapy. Conversely, LLC cells had high basal expression of Socs1, an inhibitor of IFNγ. Silencing Socs1 increased response to IFNγ in vitro and sensitized tumors to anti-PD-1. This was associated with a reshaped TME, characterized by enhanced T cell infiltration and enrichment of PD-L1 high myeloid cells. These studies demonstrate that targeted enhancement of tumor-intrinsic IFNγ signaling can induce of cascade of changes associated with increased therapeutic vulnerability.SummaryMechanisms regulating response to anti-PD-1 therapy in lung cancer are not well defined. This study, using orthotopic immunocompetent mouse models of lung cancer, demonstrates that intrinsic sensitivity of cancer cells to IFNγ determines anti-PD-1 responsiveness through alterations in the tumor microenvironment.

scholarly journals S100A2 induces the growth of Calu-6 Lung Cancer Cells via apoptosis inhibition, invasion enhancement and promoting cell division

2019 ◽  
Author(s):  
Ting Wang ◽  
Yiqian Liang ◽  
Asmitananda Thakur
Keyword(s):  
Lung Cancer ◽  
Cell Division ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Lung Cancer Cell ◽  
Lung Cancer Patients ◽  
Apoptosis Inhibition

Abstract Background S100 calcium binding protein A2 (S100A2) has been confirmed to have an abnormal expression in lung cancer and is associated with a better disease-free internal of lung cancer patients. Our previous studies on S100A2 in lung cancer concentrated on the clinical roles of this protein in lung cancer, finding that S100A2 increasingly expressed in the sera, tissues and plural effusion of lung cancer patients. This study emphasizes its value in the lung cancer cell line.Methods We constructed a S100A2 expression lentivirus vector, then transfected it and blank vector into the Calu-6 lung cancer cell line respectively. After the successful transfection, (which was confirmed by RT-PCR and Western-blot), we used MTT, transwell and flow cytometric analysis to compare the differences in cell proliferation, cell migration, cell invasion, cell apoptosis and cell cycle among the three groups (Calu-6, Calu/neo, Calu-6/S100A2).Results Calu-6 lung cancer cells showed a shift from G1 to S phase after being transfected with S100A2, compared with the control groups. Additionally, Calu-6/S1000A2 cells had enhanced abilities of invasion and down-abilities of apoptosis in contrast with the blank groups (P<0.05). However, there were no significant difference among these three group in the cell behaviors of migration and proliferation (P>0.05).Conclusion Our results firstly indicate that S100A2 has a positive influence on the biological characteristics of Calu-6 lung cancer cell line, including cell division, invasion and apoptosis inhibition. It may play a significant role in the genesis and progression of lung cancer.

scholarly journals The protein kinase MAP3K19 phosphorylates MAP2Ks and thereby activates ERK and JNK kinases and increases viability of KRAS-mutant lung cancer cells

2020 ◽  
Vol 295 (25) ◽  
pp. 8470-8479
Author(s):  
Van T. Hoang ◽  
Katherine Nyswaner ◽  
Pedro Torres-Ayuso ◽  
John Brognard
Keyword(s):  
Lung Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Mapk Kinase ◽  
Pathway Activation ◽  
Erk Kinase

Identifying additional mitogen-activated protein kinase (MAPK) pathway regulators is invaluable in aiding our understanding of the complex signaling networks that regulate cellular processes, including cell proliferation and survival. Here, using in vitro kinase assays and by expressing WT or kinase-dead MAPK kinase kinase 19 (MAP3K19) in the HEK293T cell line and assessing activation of the extracellular signal–regulated kinase (ERK) and JUN N-terminal kinase (JNK) signaling pathways, we defined MAP3K19 as a novel regulator of MAPK signaling. We also observed that overexpression of WT MAP3K19 activates both the ERK and JNK pathways in a panel of cancer cell lines. Furthermore, MAP3K19 sustained ERK pathway activation in the presence of inhibitors targeting the RAF proto-oncogene Ser/Thr protein kinase (RAF) and MAPK/ERK kinase, indicating that MAP3K19 activates ERK via a RAF-independent mechanism. Findings from in vitro and in-cell kinase assays demonstrate that MAP3K19 is a kinase that directly phosphorylates both MAPK/ERK kinase (MEK) and MAPK kinase 7 (MKK7). Results from an short-hairpin RNA screen indicated that MAP3K19 is essential for maintaining survival in KRAS-mutant cancers; therefore, we depleted or inhibited MAP3K19 in KRAS-mutant cancer cell lines and observed that this reduces viability and decreases ERK and JNK pathway activation. In summary, our results reveal that MAP3K19 directly activates the ERK and JNK cascades and highlight a role for this kinase in maintaining survival of KRAS-mutant lung cancer cells.

Evaluation of the in vitro Chemosensitivity and Correlation with Clinical Outcomes in Lung Cancer using the ATP-TCA

2018 ◽  
Vol 18 (1) ◽  
pp. 139-145 ◽  
Author(s):  
Zhiyao Chen ◽  
Shichao Zhang ◽  
Sheng Ma ◽  
Chang Li ◽  
Chun Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Lung Cancer Patients ◽  
In Vitro Chemosensitivity

Background and Objective: Multiple drug resistance (MDR) to chemotherapeutic agents often leads to a failure to respond to chemotherapy. We utilized an in vitro chemosensitivity test to identify sensitive and effective chemotherapeutic drugs and further elucidated the correlation between the in vivo chemosensitivity and clinical outcomes. Methods: Here, we evaluated the in vitro chemosensitivity and MDR of 120 lung cancer patients to eight singledrug chemotherapies and of 291 lung cancer patients to seven chemotherapy regimens using an ATP-based tumor chemosensitivity assay (ATP-TCA). Additionally, the chemosensitivity profiles of lung adenocarcinoma patients (284 cases) and lung squamous cell carcinoma patients (90 cases) to these single-drug and chemotherapy regimens were compared. Furthermore, the correlations between the chemosensitivity and clinical outcomes were investigated in 16 stage III squamous cell carcinoma patients. Results and Conclusion: PTX (51.7%), TXT (43.3%), GEM (12.5%), PTX+DDP (62.5%), TXT+L-OHP (54.3%) and VP-16+DDP (16.2%) had the highest in vitro chemosensitivity rates. Approximately 31.7% of patients developed resistance to all eight single-drug chemotherapies, and 25.8% of patients displayed resistance to all seven chemotherapy regimens. In addition, lung squamous cell carcinoma was significantly more sensitive to GEM and MTA+DDP than lung adenocarcinoma (P<0.05). Further analysis showed that patients with higher drug sensitivity tended to have longer disease-free survival (18 months vs. 8.5 months) than patients displaying drug resistance (P<0.05). These results suggest that the implementation of in vitro drug susceptibility testing before chemotherapy can effectively prevent the occurrence of primary drug resistance and inappropriate drug treatment.

scholarly journals Multiphasic modelling and computation of metastatic lung-cancer cell proliferation and atrophy in brain tissue based on experimental data

2021 ◽  
Author(s):  
Wolfgang Ehlers ◽  
Markus Morrison ◽  
Patrick Schröder ◽  
Daniela Stöhr ◽  
Arndt Wagner
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Interstitial Fluid ◽  
Metastatic Cancer ◽  
Cancer Growth ◽  
Human Beings ◽  
Stress And Deformation ◽  
The Brain

AbstractCancer is one of the most serious diseases for human beings, especially when metastases come into play. In the present article, the example of lung-cancer metastases in the brain is used to discuss the basic problem of cancer growth and atrophy as a result of both nutrients and medication. As the brain itself is a soft tissue that is saturated by blood and interstitial fluid, the biomechanical description of the problem is based on the Theory of Porous Media enhanced by the results of medication tests carried out in in-vitro experiments on cancer-cell cultures. Based on theoretical and experimental results, the consideration of proliferation, necrosis and apoptosis of metastatic cancer cells is included in the description by so-called mass-production terms added to the mass balances of the brain skeleton and the interstitial fluid. Furthermore, the mass interaction of nutrients and medical drugs between the solid and the interstitial fluid and its influence on proliferation, necrosis and apoptosis of cancer cells are considered. As a result, the overall model is appropriate for the description of brain tumour treatment combined with stress and deformation induced by cancer growth in the skull.

scholarly journals New Role of Red Blood Cells in Absorption of DNA Bearing Tumorigenic Mutations from Lung Cancer Tissue

2021 ◽  
Author(s):  
Nai-Xin Liang ◽  
Tao Wang ◽  
Cong Zhang ◽  
Zichen Jiao ◽  
Tianqiang Song ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Red Blood Cells ◽  
Cancer Cell ◽  
Blood Cells ◽  
Early Stage ◽  
Digital Pcr ◽  
Cancer Tissue ◽  
Lung Cancer Patients

AbstractRed blood cells (RBC) are commonly assumed to be vehicles for oxygen, carbon dioxide, and cells’ metabolic byproducts. In this study, we investigated whether RBC may contain cancer-cell derived DNA and whether such cargo may be used as a biomarker for detecting cancer. Using an in vitro co-culture system, we showed that RBC could absorb DNA bearing tumorigenic mutations from cancer cell lines. Next, we demonstrated that we could detect common genetic mutations, including EGFR 19 deletion, L858R, and KRAS G12 in RBC collected from early-stage non-small cell lung cancer patients. We were able to repeat our finding using both next-generation sequencing and droplet digital PCR. Our study highlights a new biological phenomenon involving RBC and their translational potential as a novel liquid biopsy technology platform that can be used for early cancer screening.

scholarly journals NUCKS Promotes the Proliferation, Migration and Invasion of Lung Cancer Cells Through Pi3k/Akt Signalling Pathway

2021 ◽  
Vol 44 (2) ◽  
pp. E55-61
Author(s):  
Cheng Hu ◽  
Qian Zha ◽  
Ping Hua ◽  
Lina Xiao ◽  
Deng Pan
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Lung Cancer Cell Line ◽  
Signalling Pathway ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Lung Cancer Cell

Purpose: Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) overexpression has been reported in various types of cancers. The purpose of this study is to clarify the role of NUCKS, underlying the involvement of non-small-cell lung cancer, in the progression of lung cancer. Methods: The small interfering ribonucleic acid (siRNA) of NUCKS was transfected into a lung cancer cell line (NCI-H460, A549, NCI-H1299 and NCI-H1975). Functional experiments (MTT assay, Annexin V-FITC/PI double staining assay, colony formation assay, wound healing assay and Transwell assay) were performed to measure the effects of NUCKS on lung cancer cell viability, migration, invasion and apoptosis. Results: NUCKS was found to be up-regulated in lung cancer cells. Knockdown of NUCKS significantly altered lung cancer cell apoptosis, proliferation colony formation, invasion and migration. Moreover, knockdown of NUCKS attenuated the activation of the PI3K/AKT pathway in lung cancer cells. Conclusion: NUCKS was overexpressed in lung cancer cells and played an important role in lung cancer by increasing cell growth through the PI3K/AKT signalling pathway. This in vitro study suggested NUCKS should be evaluated in a clinical setting as a novel biomarker and potential therapeutic target for lung cancer.

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