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platelet activation,cancer

Li-Huang Zha, Jun Zhou, Tang-Zhiming Li, Hui Luo, Men-Qiu Zhang, Sheng Li, Zai-Xin Yu
Phosphoinositide 3-kinase (PI3K) activation plays a critical role in the pulmonary vascular remodeling of pulmonary hypertension (PH). The nucleotide-oligomerization domain (NOD)-like receptor subfamily C3 (NLRC3) inhibits proliferation and inflammation via PI3K signaling in cancer. We previously showed NLRC3 was significantly reduced in PH patients, but the mechanism of function remains unclear. This study aimed to determine the potential role of NLRC3 in PH. We found that NLRC3 was downregulated in the pulmonary arteries of PH animal models and platelet-derived growth factor-BB (PDGF-BB) stimulated pulmonary arterial smooth muscle cells (PASMCs)...
February 14, 2019: Journal of Cellular Physiology
Jing Wang, Yizhuo Zhao, Qiming Wang, Li Zhang, Jianhua Shi, Zhehai Wang, Ying Cheng, Jianxing He, Yuankai Shi, Hao Yu, Yang Zhao, Weiqiang Chen, Yi Luo, Xiuwen Wang, Kejun Nan, Faguang Jin, Jian Dong, Baolan Li, Zhujun Liu, Baohui Han, Kai Li
Objective: Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-Kit, and c-MET; therefore, it exhibits both antitumor and anti-angiogenetic activities. A phase III trial has shown that anlotinib improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC), who presented with progressive disease or intolerance after standard chemotherapy...
November 2018: Cancer Biology & Medicine
Anne-Laure Papa, Amanda Jiang, Netanel Korin, Michelle B Chen, Erin T Langan, Anna Waterhouse, Emma Nash, Jildaz Caroff, Amanda Graveline, Andyna Vernet, Akiko Mammoto, Tadanori Mammoto, Abhishek Jain, Roger D Kamm, Matthew J Gounis, Donald E Ingber
Platelets are crucial for normal hemostasis; however, their hyperactivation also contributes to many potentially lethal pathologies including myocardial infarction, stroke, and cancer. We hypothesized that modified platelets lacking their aggregation and activation capacity could act as reversible inhibitors of platelet activation cascades. Here, we describe the development of detergent-extracted human modified platelets (platelet decoys) that retained platelet binding functions but were incapable of functional activation and aggregation...
February 13, 2019: Science Translational Medicine
Saleh Rachidi, Maneet Kaur, Tim Lautenschlaeger, Zihai Li
Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality...
February 13, 2019: Platelets
Shannon Kispert, John Marentette, Jane McHowat
Cigarette smoking is the number one risk factor for bladder cancer development and epidemiological data suggest that nearly half of all bladder cancer patients have a history of smoking. In addition to stimulating the growth of a primary tumor, it has been shown that there is a correlation between smoking and tumor metastasis. Platelet activating factor (PAF) is expressed on the cell surface of the activated endothelium and, through binding with the PAF-receptor (PAF-R), facilitates transendothelial migration of cells in the circulation (McHowat et al...
February 2019: Physiological Reports
Ya-Ling Hsu, Meng-Chi Yen, Wei-An Chang, Pei-Hsun Tsai, Yi-Chung Pan, Ssu-Hui Liao, Po-Lin Kuo
BACKGROUND: Metastasis is the major cause of death from breast cancer. Colonization and adaption of metastatic cells in distant organs is a rate-limiting step of the cancer spreading. The underlying mechanisms responsible for the colonization of breast cancer to lung metastatic niches are not fully understood. METHODS: Specific gene contributions to lung metastasis were identified by comparing gene profiles of 4T1 tumors metastasizing to various organs via microarray...
February 12, 2019: Breast Cancer Research: BCR
Lewis S C Ward, Lozan Sheriff, Jennifer L Marshall, Julia E Manning, Alexander Brill, Gerard B Nash, Helen M McGettrick
Mesenchymal stromal cells (MSC) up-regulate podoplanin at sites of infection, chronic inflammation, and cancer. We investigated the functional consequences of podoplanin expression on the migratory potential of MSC and their interactions with circulating platelets. Expression of podoplanin significantly enhanced the migration of MSC compared to MSC lacking podoplanin. Rac-1 inhibition altered the membrane localisation of podoplanin and in turn significantly reduced MSC migration. Blocking Rac-1 activity had no effect on the migration of MSC lacking podoplanin, indicating it was responsible for regulation of migration through podoplanin...
February 11, 2019: Journal of Cell Science
Miguel Quintanilla, Lucía Montero-Montero, Jaime Renart, Ester Martín-Villar
Podoplanin is a small cell-surface mucin-like glycoprotein that plays a crucial role in the development of the alveoli, heart, and lymphatic vascular system. Emerging evidence indicates that it is also involved in the control of mammary stem-cell activity and biogenesis of platelets in the bone marrow, and exerts an important function in the immune response. Podoplanin expression is upregulated in different cell types, including fibroblasts, macrophages, T helper cells, and epithelial cells, during inflammation and cancer, where it plays important roles...
February 6, 2019: International Journal of Molecular Sciences
Rosalia Grande, Melania Dovizio, Simone Marcone, Paulina B Szklanna, Annalisa Bruno, H Alexander Ebhardt, Hilary Cassidy, Fionnuala Ní Áinle, Anna Caprodossi, Paola Lanuti, Marco Marchisio, Geltrude Mingrone, Patricia B Maguire, Paola Patrignani
Rationale: Obesity is a risk factor for atherothrombosis and various cancers. However, the mechanisms are not yet completely clarified. Objectives: We aimed to verify whether the microparticles (MPs) released from thrombin-activated platelets differed in obese and non-obese women for number, size, and proteomics cargo and the capacity to modulate in vitro the expression of (i) genes related to the epithelial to mesenchymal transition (EMT) and the endothelial to mesenchymal transition (EndMT), and (ii) cyclooxygenase (COX)-2 involved in the production of angiogenic and inflammatory mediators...
2019: Frontiers in Pharmacology
Ronan Lordan, Alexandros Tsoupras, Ioannis Zabetakis
Cancer is the second leading cause of mortality worldwide. The role of unresolved inflammation in cancer progression and metastasis is well established. Platelet-activating factor (PAF) is a key proinflammatory mediator in the initiation and progression of cancer. Evidence suggests that PAF is integral to suppression of the immune system and promotion of metastasis and tumor growth by altering local angiogenic and cytokine networks. Interactions between PAF and its receptor may have a role in various digestive, skin, and hormone-dependent cancers...
February 5, 2019: Advances in Nutrition
Yusuke Higashi, Srinivas Mummidi, Sergiy Sukhanov, Tadashi Yoshida, Makoto Noda, Patrice Delafontaine, Bysani Chandrasekar
Minocycline, a tetracycline antibiotic, is known to exert vasculoprotective effects independent of its anti-bacterial properties; however the underlying molecular mechanisms are not completely understood. Reversion Inducing Cysteine Rich Protein with Kazal Motifs (RECK) is a cell surface expressed, membrane anchored protein, and its overexpression inhibits cancer cell migration. We hypothesized that minocycline inhibits platelet-derived growth factor (PDGF)-induced human aortic smooth muscle cell (SMC) proliferation and migration via RECK upregulation...
February 1, 2019: Cellular Signalling
Silvia Sookoian, Carlos J Pirola
BACKGROUND/AIM: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Characterised by abnormal fat accumulation in the liver, NAFLD presents high degree of comorbidity with disorders of the Metabolic syndrome, including type 2 diabetes, obesity and cardiovascular disease. These comorbidities have strong negative impact on the natural course of NAFLD and vice versa, whereby the presence of NAFLD substantially modifies the course and prognosis of Metabolic syndrome-associated diseases...
February 4, 2019: Alimentary Pharmacology & Therapeutics
Yue Jing, Yue Jin, Yujia Wang, Sheng Chen, Xiaoxin Zhang, Yuxian Song, Zhiyong Wang, Yumei Pu, Yanhong Ni, Qingang Hu
Oral squamous cell carcinoma (OSCC) is a highly lethal cancer in the world, and the prognosis of OSCC is poor with a 60% 5-year survival rate in recent decades. Here, we introduced a novel secretory and acid glycoprotein with cysteine rich (secreted protein acidic and rich in cysteine, SPARC), which is correlated with the worst pattern of invasion (WPOI) and prognosis of OSCC. SPARC expression levels were measured in OSCC tissues and normal tissues using quantitative polymerase chain reaction and immunohistochemistry...
January 31, 2019: Journal of Cellular Physiology
Ying Zhu, Yongyue Wei, Ruyang Zhang, Xuesi Dong, Sipeng Shen, Yang Zhao, Jianling Bai, Demetrius Albanes, Neil E Caporaso, Maria Teresa Landi, Bin Zhu, Stephen J Chanock, Fangyi Gu, Stephen Lam, Ming-Sound Tsao, Frances A Shepherd, Adonina Tardon, Ana Fernández-Somoano, Guillermo Fernandez-Tardon, Chu Chen, Matthew J Barnett, Jennifer Doherty, Stig E Bojesen, Mattias Johansson, Paul Brennan, James D McKay, Robert Carreras-Torres, Thomas Muley, Angela Risch, Heunz-Erich Wichmann, Heike Bickeboeller, Albert Rosenberger, Gad Rennert, Walid Saliba, Susanne M Arnold, John K Field, Michael P A Davies, Michael W Marcus, Xifeng Wu, Yuanqing Ye, Loic Le Marchand, Lynne R Wilkens, Olle Melander, Jonas Manjer, Hans Brunnström, Rayjean J Hung, Geoffrey Liu, Yonathan Brhane, Linda Kachuri, Angeline S Andrew, Eric J Duell, Lambertus A Kiemeney, Erik H F M van der Heijden, Aage Haugen, Shanbeh Zienolddiny, Vidar Skaug, Kjell Grankvist, Mikael Johansson, Penella J Woll, Angela Cox, Fiona Taylor, Dawn M Teare, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Richard S Houlston, John McLaughlin, Victoria L Stevens, Hongbing Shen, Zhibin Hu, Juncheng Dai, Christopher I Amos, Younghun Han, Dakai Zhu, Gary E Goodman, Feng Chen, David C Christiani
BACKGROUND: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. METHODS: We performed single and combined multiple instrumental variable Mendelian Randomization(MR) analysis by an inverse-weighted (IVW) method, in addition to a series of sensitivity analyses. Summary data for associations between single nucleotide polymorphisms (SNPs) and platelet count is from a recent publication including 48,666 Caucasian Europeans and International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls analyze associations between candidate single nucleotide polymorphisms and lung cancer risk...
January 30, 2019: Cancer Epidemiology, Biomarkers & Prevention
Shuyin Duan, Na Wang, Li Huang, Hua Shao, Peng Zhang, Wei Wang, Yongjun Wu, Jing Wang, Hong Liu, Qiao Zhang, Feifei Feng
Inflammatory microenvironment has been found as a new characteristic of cancer; however, the mechanisms of inflammation-related lung cancer remain unclear. To explore the role of NLRP3 inflammsome activation in inflammation-related lung carcinogenesis, a cell model was set up. Human bronchial epithelial cells (BEAS-2B) were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 24 hours, and then treated with 2.4 μg/mL coal tar pitch extract (CTPE) for 24 hours, after removal of LPS and CTPE, the cells were numbered passage 1 and were passaged and treated in this way until passage 30, which was called LPS + CTPE group...
January 30, 2019: Environmental Toxicology
Shuo Miao, Dan Shu, Ying Zhu, Meng Lu, Qingsong Zhang, Youliang Pei, Ao-Di He, Rong Ma, Bixiang Zhang, Zhang-Yin Ming
Tumor-associated thrombosis is the second leading risk factor for cancer patient death, and platelets activity is abnormal in cancer patients. Discovering the mechanism of platelet activation and providing effective targets for therapy are urgently needed. Cancer cell- derived IgG has been reported to regulate development of tumors. However, studies on the functions of cancer cell-derived IgG are quite limited. Here we investigated the potential role of cancer cell-derived IgG in platelet activation. We detected the expression of CD62P on platelets by flow cytometry and analyzed platelet function by platelets aggregation and ATP release...
January 28, 2019: Cell Death & Disease
Dursun Fırat Ergül, Mehtap Pehlivanlar Küçük, Özgür Kömürcü, Fatma Ülger
IgG4-related disease (IgG4-RD) is a set of diseases that can affect multiple organs, produce an immune-mediated fibroinflammatory response, and lead to tissue destruction and organ failure. Hemophagocytic syndrome is a life-threatening hyperinflammatory fatal disease caused by defect and excessive macrophage activity in natural killer cells. The disease can often be confused with other immune-mediated diseases such as cancer, infection, interstitial lung disease, sjogren's syndrome, wegener's vasculitis, or temporal arteritis...
December 2018: Tüberküloz Ve Toraks
Kelly E Johnson, Julia R Ceglowski, Harvey G Roweth, Jodi A Forward, Mason D Tippy, Saleh El-Husayni, Rajesh Kulenthirarajan, Michael W Malloy, Kellie R Machlus, Wendy Y Chen, Joseph E Italiano, Elisabeth M Battinelli
It is now recognized that compounds released from tumor cells can activate platelets, causing the release of platelet-derived factors into the tumor microenvironment. Several of these factors have been shown to directly promote neovascularization and metastasis, yet how the feedback between platelet releasate and the tumor cell affects metastatic phenotype remains largely unstudied. Here, we identify that breast tumor cells secrete high levels of interleukin 8 (IL-8, CXCL8) in response to platelet releasate, which promotes their invasive capacity...
January 22, 2019: Blood Advances
Xiaoyan Si, Li Zhang, Hanping Wang, Xiaotong Zhang, Mengzhao Wang, Baohui Han, Kai Li, Qiming Wang, Jianhua Shi, Zhehai Wang, Ying Cheng, Yuankai Shi, Weiqiang Chen, Xiuwen Wang, Yi Luo, Kejun Nan, Faguang Jin
BACKGROUND: Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, and stem cell factor receptor (c-Kit). In the phase III ALTER-0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non-small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens...
January 21, 2019: Thoracic Cancer
Brigette Church, Erika Wall, John R Webb, Caroline E Cameron
Extracellular bacteria that spread via the vasculature employ invasive mechanisms that mirror those of metastatic tumor cells, including intravasation into the bloodstream and survival during hematogenous dissemination, arrestation despite blood flow, and extravasation into distant tissue sites. Several invasive bacteria have been shown to exploit normal platelet function during infection. Due to their inherent ability to interact with and influence other cell types, platelets play a critical role in alteration of endothelial barrier permeability, and their role in cancer metastasis has been well established...
2019: PloS One
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