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Cancer microenvironment

Derek M van Pel, Kaori Harada, Dandan Song, Christian C Naus, Wun Chey Sin
Glioma is a highly aggressive form of brain cancer, with some subtypes having 5-year survival rates of less than 5%. Tumour cell invasion into the surrounding parenchyma seems to be the primary driver of these poor outcomes, as most gliomas recur within 2 cm of the original surgically-resected tumour. Many current approaches to the development of anticancer therapy attempt to target genetic weaknesses in a particular cancer, but may not take into account the microenvironment experienced by a tumour and the patient-specific genetic differences in susceptibility to treatment...
June 16, 2018: Journal of Cell Communication and Signaling
Manuel U Ramirez, Elizabeth R Stirling, Nancy J Emenaker, David D Roberts, David R Soto-Pantoja
The metabolism of arachidonic acid and other polyunsaturated fatty acids produces eicosanoids, a family of biologically active lipids that are implicated in homeostasis and in several pathologies that involve inflammation. Inflammatory processes mediated by eicosanoids promote carcinogenesis by exerting direct effects on cancer cells and by affecting the tumor microenvironment. Therefore, understanding how eicosanoids mediate cancer progression may lead to better approaches and chemopreventive strategies for the treatment of cancer...
June 16, 2018: Cancer Metastasis Reviews
Eleni-Anastasia Triantafyllou, Eleni Georgatsou, Ilias Mylonis, George Simos, Efrosyni Paraskeva
Hypoxia inducible factor-1 (HIF-1) supports survival of normal cells under low oxygen concentration and cancer cells in the hypoxic tumor microenvironment. This involves metabolic reprogramming via upregulation of glycolysis, downregulation of oxidative phosphorylation and, less well documented, effects on lipid metabolism. To investigate the latter, we examined expression of relevant enzymes in cancer cells grown under hypoxia. We show that expression of acylglycerol-3-phosphate acyltransferase 2 (AGPAT2), also known as lysophosphatidic acid acyltransferase β (LPAATβ), was upregulated under hypoxia and this was impaired by siRNA-mediated knockdown of HIF-1α...
June 14, 2018: Biochimica et Biophysica Acta
Ulrike G Glaser, Joachim Fandrey
Hypoxia due to rapid tumor growth with impaired neovascularization and inflammation resulting from immune cell activation are hallmarks of cancer. Hypoxia-inducible factors (HIFs) control transcriptional adaptation in response to low oxygen conditions, both in tumor and immune cells. In addition, sphingolipids become increasingly recognized as important cell mediators in tumor and inflammatory hypoxia. Recent studies have identified acid sphingomyelinase (ASM), a central enzyme in the sphingolipid metabolism, as a regulator of several types of stress stimuli pathways and an important player in the tumor microenvironment...
June 1, 2018: Biological Chemistry
Yu-Ling Tai, Ko-Chien Chen, Jer-Tsong Hsieh, Tang-Long Shen
Exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and varied cells in the local and distant microenvironments. Such intercellular cross-talks result in changes in multiple cellular and biological functions in recipient cells. Several hallmarks of cancer have been reportedly impacted by this exosome-mediated cell-to-cell communication, including modulating immune responses, re-programming stromal cells, re-modeling the architecture of extracellular matrix, or even endowing cancer cells with characteristics of drug resistance...
June 16, 2018: Cancer Science
Sander C Steenbeek, Thang V Pham, Joep de Ligt, Anoek Zomer, Jaco C Knol, Sander R Piersma, Tim Schelfhorst, Rick Huisjes, Raymond M Schiffelers, Edwin Cuppen, Connie R Jimenez, Jacco van Rheenen
Recent data showed that cancer cells from different tumor subtypes with distinct metastatic potential influence each other's metastatic behavior by exchanging biomolecules through extracellular vesicles (EVs). However, it is debated how small amounts of cargo can mediate this effect, especially in tumors where all cells are from one subtype, and only subtle molecular differences drive metastatic heterogeneity. To study this, we have characterized the content of EVs shed in vivo by two clones of melanoma (B16) tumors with distinct metastatic potential...
June 14, 2018: EMBO Journal
Jing Liu, Jia-Xin Shen, Hua-Tao Wu, Xiao-Li Li, Xiao-Fen Wen, Cai-Wen Du, Guo-Jun Zhang
PURPOSE: Extracellular matrix (ECM) is an important component of tumor microenvironment and plays critical roles in cancer development and metastasis, in which collagen is the major structural protein. Collagen type I alpha 1 (COL1A1) is reportedly associated with the development of several human diseases. However, the functions and mechanisms of cellular expression of COL1A1 in breast cancer remain unknown. The purpose of this study is to investigate the cellular expression of COL1A1 in breast cancer cells and patients, and its role in the development and metastasis of breast cancer...
May 2018: Discovery Medicine
Catherine J Libby, Sixue Zhang, Gloria A Benavides, Sarah E Scott, Yanjie Li, Matthew Redmann, Anh Nhat Tran, Arphaxad Otamias, Victor Darley-Usmar, Marek Napierala, Jianhua Zhang, Corinne Elizabeth Augelli-Szafran, Wei Zhang, Anita B Hjelmeland
Tumor heterogeneity has hampered the development of novel effective therapeutic options for aggressive cancers, including the deadly primary adult brain tumor glioblastoma (GBM). Intratumoral heterogeneity is partially attributed to the tumor initiating cell (TIC) subset that contains highly tumorigenic, stem-like cells. TICs display metabolic plasticity but can have a reliance on aerobic glycolysis. Elevated expression of GLUT1 and GLUT3 is present in many cancer types, with GLUT3 being preferentially expressed in brain TICs (BTICs) to increase survival in low nutrient tumor microenvironments, leading to tumor maintenance...
June 15, 2018: ACS Chemical Biology
Agata Mlynska, Egle Povilaityte, Inga Zemleckaite, Karolina Zilionyte, Marius Strioga, Jan Krasko, Neringa Dobrovolskiene, Mei-Wen Peng, Birute Intaite, Vita Pasukoniene
PROBLEM: Development of platinum resistance in ovarian cancer is mediated by both cancer cells and tumor microenvironment. Activation of epithelial-mesenchymal transition program in cancer cells may lead to enrichment for resistant clones. These processes can be affected by tumor-associated macrophages, a highly plastic population of cells that participate in tumor progression and response to treatment by shaping the microenvironment. We aimed to study how platinum resistance influences the crosstalk between macrophages and ovarian cancer cells...
June 14, 2018: American Journal of Reproductive Immunology: AJRI
Peng Wu, Guihao Zhang, Jie Zhao, Jiawei Chen, Yang Chen, Weina Huang, Jialei Zhong, Jiarong Zeng
Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported...
2018: Frontiers in Cellular and Infection Microbiology
Jun Zhang, Yue Wu, Yu-Hang Lin, Shuai Guo, Pei-Fang Ning, Zhi-Chao Zheng, Yue Wang, Yan Zhao
AIM: To investigate the relationship between hypoxia-inducible factor-1α (HIF-1α), prolyl 4-hydroxylase beta (P4HB) expression, and clinicopathologic parameters, as well as the prognostic value of these genes for patients with gastric cancer (GC). METHODS: Hypoxia is a critical factor that shapes the GC microenvironment. In previous reports, we have demonstrated that P4HB is a potential target of HIF-1α. In the present study, gene expression profiling interactive analysis (GEPIA) was used to analyze the relationship between P4HB and hypoxia-associated genes...
June 14, 2018: World Journal of Gastroenterology: WJG
Uilst Bat-Erdene, Eric Quan, Kelvin Chan, Brianna-Marie Lee, Wejdan Matook, Ki-Young Lee, Jesusa L Rosales
A proliferation-inducing ligand (APRIL), which induces survival and migration signals and tumor growth, is commonly observed in breast cancer tissues but is not often expressed in breast cancer cells themselves. Here, we examined whether breast cancer cells induce APRIL secretion from neutrophils, which are frequently recruited into the breast tumor microenvironment. We found that breast cancer cells do stimulate neutrophils to secrete APRIL through their glycosaminoglycans. Breast cancer cells depleted of heparan sulfate or chondroitin sulfate glycosaminoglycans lose their ability to induce APRIL secretion from neutrophils, and heparan sulfate and chondroitin sulfate can induce secretion that is comparable to that of breast cancer cell-induced secretion...
June 15, 2018: Oncogenesis
Konstantin Stoletov, Lian Willetts, Robert J Paproski, David J Bond, Srijan Raha, Juan Jovel, Benjamin Adam, Amy E Robertson, Francis Wong, Emma Woolner, Deborah L Sosnowski, Tarek A Bismar, Gane Ka-Shu Wong, Andries Zijlstra, John D Lewis
Metastasis is the most lethal aspect of cancer, yet current therapeutic strategies do not target its key rate-limiting steps. We have previously shown that the entry of cancer cells into the blood stream, or intravasation, is highly dependent upon in vivo cancer cell motility, making it an attractive therapeutic target. To systemically identify genes required for tumor cell motility in an in vivo tumor microenvironment, we established a novel quantitative in vivo screening platform based on intravital imaging of human cancer metastasis in ex ovo avian embryos...
June 14, 2018: Nature Communications
Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart
Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors...
June 14, 2018: Cancers
Derek J Erstad, Mozhdeh Sojoodi, Martin S Taylor, Sarani Ghoshal, Allen A Razavi, Katherine A Graham-O'Regan, Nabeel Bardeesy, Cristina R Ferrone, Michael Lanuti, Peter Caravan, Kenneth K Tanabe, Bryan C Fuchs
INTRODUCTION: Syngeneic, immunocompetent allograft tumor models recapitulate important aspects of the tumor microenvironment and have short tumor latency with predictable growth kinetics, making them useful for trialing novel therapeutics. We describe surgical techniques for orthotopic and heterotopic PDAC tumor implantation and characterize phenotypes based on implantation site. METHODS: Mice (n=8 per group) were implanted with 104 cells in the pancreas or flank...
June 14, 2018: Disease Models & Mechanisms
Yuanyuan Yang, Qiling Chen, Siyu Li, Wen Ma, Guangyu Yao, Fei Ren, Zheng Cai, Peng Zhao, Guochao Liao, Jingyuan Xiong, Zhiqiang Yu
Despite the great achievements of nanomedicines made in cancer chemotherapy, precise tumor targeting and deep penetration are still major challenges. Many nanomedicines can only passively accumulate near leaky site of tumor vessels through the enhanced permeability and retention (EPR) effect and cannot reach the deep region of tumor. To improve the tumor targeting, penetration and retention efficiency, an iRGD-mediated and enzyme-induced precise targeting gold nanoparticles system (iRGD/AuNPs-A&C) was developed by simply coadministering a tumor-homing penetration peptide iRGD (CRGDKGPDC) with a legumain responsive aggregable gold nanoparticle (AuNPs-A&C)...
August 1, 2018: Journal of Biomedical Nanotechnology
Demi S Houg, Maarten F Bijlsma
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies to date, largely because it is associated with high metastatic risk. Pancreatic tumors have a characteristic tendency to metastasize preferentially to the liver. Over the past two decades, it has become evident that the otherwise hostile milieu of the liver is selectively preconditioned at an early stage to render it more conducive to the engraftment and growth of disseminated cancer cells, a concept defined as pre-metastatic niche (PMN) formation...
June 14, 2018: Molecular Cancer
Caiyun Liu, Like Qu, Chuanke Zhao, Chengchao Shou
BACKGROUND: Increasing evidence reveals a significant correlation between gamma-synuclein (SNCG) level and tumor invasion and metastasis in various human cancers. Our previous investigation showed that SNCG could secrete into extracellular environment and promoted tumor cell motility, but the mechanism is unknown. METHODS: The membrane binding ability of SNCG was characterized by immunohistochemical staining, immunofluorescence staining and fractionation of colorectal cancer (CRC) cell membrane...
June 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
Li Sun, Qianqian Wang, Bin Chen, Yuanyaun Zhao, Bo Shen, Xinlong Wang, Miaolin Zhu, Zhuqian Li, Xiangdong Zhao, Changgen Xu, Zhihong Chen, Mei Wang, Wenrong Xu, Wei Zhu
Several studies show that mesenchymal stem cells (MSCs) homing to tumors not only provide the microenvironment for tumor cells, but also promote tumor growth and metastasis. However, the exact mechanism remains unclear. Our study aims to investigate the role of gastric cancer MSCs (GCMSCs) derived IL15 during GC progression. The effects of IL15 secreted by GCMSCs on GC development were evaluated by detecting the stemness, epithelial-mesenchymal transition (EMT) and migration abilities of GC cell lines. The expression of IL15 in serum and tissues of GC patients was also assessed...
June 14, 2018: Stem Cells and Development
Jiao Chen, Bomiao Cui, Yaping Fan, Xiaoying Li, Qian Li, Yue Du, Yun Feng, Ping Zhang
Protein kinase D1 (PKD1), one of the protein kinase D (PKD) family members, plays a prominent role in multiple bio-behaviors of cancer cells. Low pH and hypoxia are unique characteristics of the tumor microenvironment. The aim of this study was to investigate the role and mechanism of PKD1 in regulating metabolism in the human tongue squamous cell carcinoma (TSCC) cell line SCC25 under a hypoxic condition, as well as growth and apoptosis. Here, we found that hypoxia not only induced the expression of HIF-1α, but also induced the expression and activation of PKD1...
June 7, 2018: Oncology Reports
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