Malignant Pleural Effusion and ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-like Cell Properties via the Vascular Endothelial Growth Factor (VEGF)/Phosphatidylinositol 3-Kinase (PI3K)/Akt/Mechanistic Target of Rapamycin (mTOR) Pathway

Yin, Tao; Wang, Guoping; He, Sisi; Shen, Guobo; Su, Chao; Zhang, Yan; Wei, Xiawei; Ye, Tinghong; Li, Ling; Yang, Shengyong; Li, Dan; Guo, Fuchun; Mo, Zeming; Wan, Yang; Ai, Ping; Zhou, Xiaojuan; Liu, Yantong; Wang, Yongsheng; Wei, Yuquan

doi:10.1074/jbc.m116.753236

Cited by 29 publications

(20 citation statements)

References 50 publications

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“…NK cells from human MPE exhibit poor cytotoxicity, having impaired degranulation and reduced perforin release. [122][123][124] In the malignant pleural environment, NK cells exhibit proangiogenic function, supporting capillary-like structures from recruited endothelial cells and produce angiogenic and vascular permeability inducing factors, including VEGF. 122 Interestingly, CD56 dim and CD56 bright NK cells isolated from human MPE cultured with IL-2 for 72 hours had potent antitumor cytolytic activity.…”

Section: Innate Immunity Within the Mpementioning

confidence: 99%

Making cold malignant pleural effusions hot: driving novel immunotherapies

et al. 2019

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Malignant pleural effusions, arising from either primary mesotheliomas or secondary malignancies, heralds advanced disease and poor prognosis. Current treatments, including therapeutic thoracentesis and tube thoracostomy, are largely palliative. The immunosuppressive environment within the pleural cavity includes myeloid derived suppressor cells, T-regulatory cells, and dysfunctional T cells. The advent of effective immunotherapy with checkpoint inhibitors and adoptive cell therapies for lung cancer and other malignancies suggests a renewed examination of local and systemic therapies for this malady. Prior strategies reporting remarkable success, including instillation of the cytokine interleukin-2, perhaps coupled with checkpoint inhibitors, should be further evaluated in the modern era.

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Section: Innate Immunity Within the Mpementioning

confidence: 99%

Making cold malignant pleural effusions hot: driving novel immunotherapies

et al. 2019

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“…MPM is preceded by up to 2 years by 'Benign Asbestos Pleural Effusion (BAPE)' (or Benign Fibrinous Pleurisy) in a significant minority of patients [114]. Since the nutritive and potentially pro-tumourigenic nature of pleural effusion has only recently been described [115], this component of early MPM biology may not have been accounted for in previous pre-clinical studies. Studies involving sequential biopsies in patients with BAPE may therefore better define the key events involved in the transition from chronic pleural inflammation to MPM, and should be considered.…”

Section: Chemoprophylaxismentioning

confidence: 99%

Progress and challenges in Mesothelioma: From bench to bedside

Blyth

Murphy

2018

Respiratory Medicine

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Malignant Pleural Mesothelioma (MPM) is currently an incurable cancer with a typical survival of 1 year from the time of diagnosis. The recent genomic and transcriptomic characterization of MPM presents new opportunities and challenges for MPM researchers. Recent advances in clinical and laboratory diagnostics, and proposals for an updated, data-driven, staging system, also present new challenges for clinicians and hospital services involved in MPM care. The aim of this review is first to introduce the reader to the topic of MPM, a disease that is causally linked to prior, typically occupational, exposure to asbestos fibres. Secondly, we will discuss MPM from the clinical and laboratory perspectives, including reviews of current and evolving therapies and our present understanding of the molecular basis of the disease. Finally, we will attempt to identify critical knowledge gaps that currently prevent more effective treatment, including the challenges involved in early detection and chemoprophylaxis.

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“…In support of this, cancer cells derived from the patients with tumors in an advanced malignant stage grow as spheroids in suspension culture conditions. 13 , 14 Recent work by several groups highlighted that anchorage-independent survival signaling universally converges into the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT. 15 – 17 In addition, EMT is also associated with tumor stemness and resistance to therapy.…”

Section: Introductionmentioning

confidence: 99%

SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage-independent growth and chemoresistance to vinblastine

Choe¹,

Kim²,

Min³

et al. 2018

OTT

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BackgroundNon-small cell lung cancer (NSCLC) is difficult to treat successfully. This intractability is mainly due to the cancer progressing through invasion, metastasis, chemotherapeutic resistance and relapse. Stemness has been linked to the various steps of cancer progression in a variety of tumors, yet little is known regarding its role in NSCLC.PurposeIn this study, we sought to determine the role of SOX2, a master regulator of pluripotency, in the growth of extracellular matrix (ECM)-detached cells during cancer progression.MethodsWe established a three-dimensional (3D) Poly-2-hydroxyethyl methacrylate (poly-HEMA) culture of lung adenocarcinoma (LUAD) A549 cells as an ECM-detached cell growth model and examined the role of stemness genes using siRNA and small molecule inhibitor in comparison to standard two dimensional (2D) culture.ResultsIn poly-HEMA culture, A549 cells formed substratum-detached spheroids with characteristics of intermediate epithelial to mesenchymal transition (EMT) and exhibited greater expression of SOX2 than did control 2D cells. Knockdown of SOX2 markedly suppressed the growth of A549 cell aggregates in poly-HEMA culture conditions and furthermore increased their sensitivity to the anticancer drug vinblastine with concomitant downregulation of the activity of the anti-apoptotic AKT kinase. Interestingly, a small molecule, RepSox, which replaces SOX2, stimulated A549 cell growth in poly-HEMA 3D culture condition.ConclusionOur findings strongly indicate that SOX2 contributes to anchorage-independent growth and chemoresistance via its downstream signaling mediator AKT kinase during the disease progression of NSCLC. SOX2 may therefore be an invaluable therapeutic target of NSCLC.

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Malignant Pleural Effusion and ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-like Cell Properties via the Vascular Endothelial Growth Factor (VEGF)/Phosphatidylinositol 3-Kinase (PI3K)/Akt/Mechanistic Target of Rapamycin (mTOR) Pathway

Cited by 29 publications

References 50 publications

Making cold malignant pleural effusions hot: driving novel immunotherapies

Making cold malignant pleural effusions hot: driving novel immunotherapies

Progress and challenges in Mesothelioma: From bench to bedside

SOX2, a stemness gene, induces progression of NSCLC A549 cells toward anchorage-independent growth and chemoresistance to vinblastine

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