scholarly journals Evaluation of Hippo Pathway and CD133 in Radiation Resistance in Small-Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Kui Yang ◽  
Yang Zhao ◽  
Yonghao Du ◽  
Ruixiang Tang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Resistance ◽  
Hippo Pathway ◽  
Small Cell ◽  
Cell Counting ◽  
Disease Stage ◽  
Small Cell Lung ◽  
The Hippo Pathway

Although the Hippo pathway and CD133 have been reported to play pertinent roles in a variety of cancer, knowledge about their contribution to radiation resistance in small-cell lung cancer (SCLC) is limited. In this first-of-a-kind study, we have reported the expression of key Hippo pathway proteins in SCLC patients by immunohistochemical staining. We assessed the involvement of yes-associated protein 1 (YAP1) in radiation resistance by Cell Counting Kit-8 (CCK-8) and flow cytometry. In addition, we analysed the impact of CD133 on radiotherapy for SCLC. The mammalian Ste20-like serine/threonine kinase 2(MST2), pMST2, and pYAP1 in the Hippo pathway were not significantly associated with the disease stage and survival time in patients with SCLC. However, the pYAP1 expression showed some significance in the “YAP/TAZ subgroup” of SCLC patients. The proportion of CD133 in the SCLC cells was controlled by the YAP1 expression. The CD133 and YAP1 levels were significantly correlation with each other in tissues of SCLC patients. We sorted and isolated the CD133+ and CD133−cells in H69 and found that the cell surface glycoprotein may be associated with the radiation resistance of SCLC.In summary, we have firstly reported the expression of key Hippo pathway proteins in SCLC patients. Furthermore, we also identified that CD133 may be controlled by the expression of YAP1 in the Hippo pathway and that CD133 may be associated with the radiation resistance of SCLC.

Knockdown of SIPA1L3 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the Hippo Pathway

2021 ◽  
Author(s):  
Si Wang ◽  
Qiang Han ◽  
Xue-Zhu Rong ◽  
Ming-Fang Sun ◽  
Ke-Xin Diao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
Hippo Pathway ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Small Cell Lung ◽  
Core Proteins ◽  
The Hippo Pathway

Abstract Background: SIPA1L3 is a member of the signal-induced proliferation-associated (SIPA) protein family, only limited data about the SIPA1L3 are currently available in human carcinoma. Our present study provides the expression pattern and function of SIPA1L3 in non-small cell lung cancer (NSCLC).Methods: We performed immunohistochemistry to detect the distribution of SIPA1L3 in NSCLC specimens and analyzed the relationship between SIPA1L3 expression and patients clinicopathological feature. We used small interfering RNA (siRNA) to specifically silence SIPA1L3, then investigated its effect on cell growth and invasion in human lung cancer cell lines. Western blot and immunoprecipitation were performed to show the interaction of SIPA1L3 with the core proteins of Hippo pathway, and the Hippo pathway activity.Results: Immunohistochemical staining showed that SIPA1L3 was cytoplasmic increasing in 147 of 217 cases. High levels of SIPA1L3 expression were associated with poor differentiation and a high tumor node metastasis stage, positive lymph nodal status, and poor prognosis. Downregulation of SIPA1L3 inhibited cell EMT, growth, and invasion. As well as SIPA1L3 inhibited Hippo pathway. SIPA1L3 interacted with AMOT, which inhibited AMOT binding to Pals, then decreased nuclear location of YAP.Conclusions: SIPA1L3 overexpression may be a marker for advanced NSCLC. SIPA1L3 reduction inhibits the proliferative and invasive ability of the lung cancer cells, which involves the Hippo pathway by contacting with AMOT.

scholarly journals Characterization of Tumor-Associated Macrophages and the Immune Microenvironment in Limited-Stage Neuroendocrine-High and -Low Small Cell Lung Cancer

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 502
Author(s):  
David Dora ◽  
Christopher Rivard ◽  
Hui Yu ◽  
Shivaun Lueke Pickard ◽  
Viktoria Laszlo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
M2 Macrophage ◽  
Strong Positive Correlation ◽  
Small Cell Lung ◽  
Limited Stage ◽  
Macrophage Marker

This study aims to characterize tumor-infiltrating macrophages (TAMs), myeloid-derived suppressor cells (MDSC), and the related molecular milieu regulating anti-tumor immunity in limited-stage neuroendocrine (NE)-high and NE-low small cell lung cancer. Primary tumors and matched lymph node (LN) metastases of 32 resected, early-stage SCLC patients were analyzed by immunohistochemistry (IHC) with antibodies against pan-macrophage marker CD68, M2-macrophage marker CD163, and MDSC marker CD33. Area-adjusted cell counting on TMAs showed that TAMs are the most abundant cell type in the TME, and their number in tumor nests exceeds the number of CD3 + T-cells (64% vs. 38% in NE-low and 71% vs. 18% in NE-high). Furthermore, the ratio of CD163-expressing M2-polarized TAMs in tumor nests was significantly higher in NE-low vs. NE-high tumors (70% vs. 31%). TAM density shows a strong positive correlation with CD45 and CD3 in tumor nests, but not in the stroma. fGSEA analysis on a targeted RNAseq oncological panel of 2560 genes showed that NE-high tumors exhibited increased enrichment in pathways related to cell proliferation, whereas in NE-low tumors, immune response pathways were significantly upregulated. Interestingly, we identified a subset of NE-high tumors representing an immune-oasis phenotype, but with a different gene expression profile compared to NE-low tumors. In contrast, we found that a limited subgroup of NE-low tumors is immune-deserted and express distinct cellular pathways from NE-high tumors. Furthermore, we identified potential molecular targets based on our expression data in NE-low and immune-oasis tumor subsets, including CD70, ANXA1, ITGB6, TP63, IFI27, YBX3 and CXCR2.

scholarly journals Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

2018 ◽  
Vol 51 (6) ◽  
pp. 2938-2954 ◽  
Author(s):  
Jing Shen ◽  
Shoubo Cao ◽  
Xin Sun ◽  
Bo Pan ◽  
Jingyan Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Cell Counting ◽  
Small Cell Lung ◽  
Sonodynamic Therapy

Background/Aims: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. Methods: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. Results: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. Conclusion: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

scholarly journals Overexpression of miRNA-21 promotes radiation-resistance of non-small cell lung cancer

2013 ◽  
Vol 8 (1) ◽  
Author(s):  
Wang Xiao-chun ◽  
Wang Wei ◽  
Zhang Zhu-Bo ◽  
Zhao Jing ◽  
Tan Xiao-Gang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Radiation Resistance ◽  
Small Cell ◽  
Small Cell Lung

Prognostic value of Platelet-to-Lymphocyte Ratio (PLR) and IL-6 in patients with small cell lung cancer

2018 ◽  
Vol 54 (3) ◽  
pp. 137-144
Author(s):  
Ewa Wójcik ◽  
Zofia Stasik ◽  
Urszula Rychlik ◽  
Jadwiga Tarapacz ◽  
Jan Kanty Kulpa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumour Marker ◽  
Small Cell ◽  
Disease Stage ◽  
Small Cell Lung ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Favourable Prognosis

Background: In order to identify patients with the most favourable prognosis, the effect of baseline level of interleukin-6 (IL-6) and platelet-to-lymphocyte ratio (PLR) on survival was analysed in patients with small cell lung cancer.<br>Material and Methods: 159 patients with small cell lung cancer were enrolled. Full blood count enabling computing the PLR, as well as NSE, ProGRP and IL-6 levels were done in all participants.<br>Results: We demonstrated significant effect of disease stage, performance status, sex, initial NSE, ProGRP and IL-6 levels as well as PLR on survival of patients with SCLC. In subgroups with normal initial levels of ProGRP (below 50.36 ng/L) and NSE (below 20.95 μg/L), the IL-6 level above 6.0 ng/L worsens the prognosis by 28% and 29%, respectively. In a subgroup with elevated initial ProGRP, the difference in survival between patients with normal vs elevated IL-6 level at baseline was 25%, whereas in a subgroup with elevated initial NSE it was 14%. The between-subgroup differences in PLR were less considerable. There was a significant effect of PLR on patient survival in a subgroup with normal initial NSE level and elevated initial ProGRP level.<br>Conclusion: In subgroups of SCLC patients identified based on initial tumour marker levels, IL-6 level can be a source of reliable prognostic information, whereas the effect of PLR is less marked. Patients with normal tumour marker levels and IL-6 below 6 ng/L at baseline have the most favourable prognosis.

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