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Cancer-associated fibroblasts

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https://www.readbyqxmd.com/read/28732355/checkpoint-kinase-1-inhibition-sensitises-transformed-cells-to-dihydroorotate-dehydrogenase-inhibition
#1
Stéphanie Arnould, Geneviève Rodier, Gisèle Matar, Charles Vincent, Nelly Pirot, Yoann Delorme, Charlène Berthet, Yoan Buscail, Jean Yohan Noël, Simon Lachambre, Marta Jarlier, Florence Bernex, Hélène Delpech, Pierre Olivier Vidalain, Yves L Janin, Charles Theillet, Claude Sardet
Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729401/jak1-stat3-activation-through-a-proinflammatory-cytokine-pathway-leads-to-resistance-to-molecularly-targeted-therapy-in-non-small-cell-lung-cancer
#2
Kazuhiko Shien, Vassiliki A Papadimitrakopoulou, Dennis Ruder, Carmen Behrens, Li Shen, Neda Kalhor, Juhee Song, J Jack Lee, Jing Wang, Ximing Tang, Roy S Herbst, Shinichi Toyooka, Luc Girard, John D Minna, Jonathan M Kurie, Ignacio I Wistuba, Julie G Izzo
Molecularly targeted drugs have yielded significant therapeutic advances in oncogene-driven non-small cell lung cancer (NSCLC), but a majority of patients eventually develop acquired resistance. Recently, the relation between proinflammatory cytokine interleukin-6 (IL6) and resistance to targeted drugs has been reported. We investigated the functional contribution of IL6 and the other members of IL6 family proinflammatory cytokine pathway to resistance to targeted drugs in NSCLC cells. In addition, we examined the production of these cytokines by cancer cells and cancer-associated fibroblasts (CAFs)...
July 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28726780/foxq1-regulates-senescence-associated-inflammation-via-activation-of-sirt1-expression
#3
Pan Wang, Cuicui Lv, Tao Zhang, Junling Liu, Jin Yang, Fangxia Guan, Tianpei Hong
Cellular senescence is an initial barrier to tumor development that prevents the proliferation of premalignant cells. However, some of the features of senescent cells seem to promote tumor progression via senescence-associated secretory phenotype (SASP). Here, we demonstrated that the protein level of forkhead box Q1 (FOXQ1), which highly overexpresses in several kinds of tumors, was significantly downregulated during both replicative and oncogene-induced senescence. Moreover, overexpression of FOXQ1 delayed senescence, whereas FOXQ1 silence led to premature senescence in human fibroblasts...
July 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28725488/generation-and-analysis-of-spheroids-from-human-primary-skin-myofibroblasts-an-experimental-system-to-study-myofibroblasts-deactivation
#4
Giuseppina Granato, Maria R Ruocco, Antonino Iaccarino, Stefania Masone, Gaetano Calì, Angelica Avagliano, Valentina Russo, Claudio Bellevicine, Gaetano Di Spigna, Giuseppe Fiume, Stefania Montagnani, Alessandro Arcucci
Myofibroblasts are activated fibroblasts involved in tissue repair and cancer. They are characterized by de novo expression of α-smooth muscle actin (α-SMA), immunoregulatory phenotype and paracrine interaction with normal and tumorigenic cells leading to cell proliferation. At the end of wound-healing myofibroblasts undergo apoptotic cell death, whereas in vitro-activated fibroblasts are also subjected to a programmed necrosis-like cell death, termed nemosis, associated with cyclooxygenase-2 (COX-2) expression induction and inflammatory response...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28723669/multicomponent-analysis-of-the-tumour-microenvironment-reveals-low-cd8-t-cell-number-low-stromal-caveolin-1-and-high-tenascin-c-and-their-combination-as-significant-prognostic-markers-in-non-small-cell-lung-cancer
#5
David Onion, Mark Isherwood, Naveen Shridhar, Mikalena Xenophontos, Madeleine L Craze, Laura J Day, María A García-Márquez, Robert G Pineda, Alexander M Reece-Smith, John H Saunders, John P Duffy, Richard H Argent
The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT)...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28718374/cancer-associated-fibroblasts-secrete-fgf-1-to-promote-ovarian-proliferation-migration-and-invasion-through-the-activation-of-fgf-1-fgfr4-signaling
#6
Yuanzhen Sun, Xiaoli Fan, Qing Zhang, Xiaoyu Shi, Guangwei Xu, Cuimin Zou
Ovarian cancer is the most lethal gynecologic malignancy, due to its high propensity for metastasis. Cancer-associated fibroblasts, as the dominant component of tumor microenvironment, are crucial for tumor progression. However, the mechanisms underlying the regulation of ovarian cancer cells by cancer-associated fibroblasts remain little known. Here, we first isolated cancer-associated fibroblasts from patients' ovarian tissues and found that cancer-associated fibroblasts promoted SKOV3 cells' proliferation, migration, and invasion...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28716525/peri-tumor-associated-fibroblasts-promote-intrahepatic-metastasis-of-hepatocellular-carcinoma-by-recruiting-cancer-stem-cells
#7
Jinghua Jiang, Fei Ye, Xue Yang, Chen Zong, Lu Gao, Yang Yang, Qiudong Zhao, Zhipeng Han, Lixin Wei
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human peri-tumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues-derived fibroblasts (CM-TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-β, HGF and VEGF...
July 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28714000/circulating-levels-of-angiogenesis-related-growth-factors-in-breast-cancer-a-study-to-profile-proteins-responsible-for-tubule-formation
#8
Gemma A Barron, Marie Goua, Klaus W J Wahle, Giovanna Bermano
The present study exploited a versatile in vitro endothelial cell/fibroblast co-culture cell system to investigate the association between angiogenesis and breast cancer by comparing the capacity of plasma from women with breast cancer and age-matched controls, to influence tubule formation and modulate angiogenesis in vitro, and to identify plasma circulating factors which might be responsible. Plasma from women with breast cancer (n=8) (added on day 7 after co-culture establishment) significantly increased tubule formation by 57% (P<0...
July 11, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28709002/exosome-rna-unshielding-couples-stromal-activation-to-pattern-recognition-receptor-signaling-in-cancer
#9
Barzin Y Nabet, Yu Qiu, Jacob E Shabason, Tony J Wu, Taewon Yoon, Brian C Kim, Joseph L Benci, Angela M DeMichele, Julia Tchou, Joseph Marcotrigiano, Andy J Minn
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28706417/indole-phytoalexin-derivatives-induce-mitochondrial-mediated-apoptosis-in-human-colorectal-carcinoma-cells
#10
Viera Tischlerova, Martin Kello, Mariana Budovska, Jan Mojzis
AIM: To investigate the mechanism of the antiproliferative effect of synthetic indole phytoalexin derivatives on human colorectal cancer cell lines. METHODS: Changes in cell proliferation and the cytotoxic effect of the tested compounds on human colorectal cancer cell lines and human fibroblasts were evaluated using MTS and BrdU assay, allowing us to choose the most potent substance. Cell cycle alterations were analyzed using flow cytometric analysis. The apoptosis-inducing effect of compound K-453 on the HCT116 cell line was examined with annexin V/PI double staining using flow cytometry, as well as acridine orange/propidium iodide (AO/PI) staining...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28706147/tumor-p38mapk-signaling-enhances-breast-carcinoma-vascularization-and-growth-by-promoting-expression-and-deposition-of-pro-tumorigenic-factors
#11
Michelle Limoge, Alfiya Safina, Alexander M Truskinovsky, Ieman Aljahdali, Justin Zonneville, Aleksandar Gruevski, Carlos L Arteaga, Andrei V Bakin
The breast carcinoma microenvironment strikingly influences cancer progression and response to therapy. Various cell types in the carcinoma microenvironment show significant activity of p38 mitogen-activated protein kinase (MAPK), although the role of p38MAPK in breast cancer progression is still poorly understood. The present study examined the contribution of tumor p38MAPK to breast carcinoma microenvironment and metastatic capacity. Inactivation of p38MAPK signaling in metastatic breast carcinoma cells was achieved by forced expression of the kinase-inactive mutant of p38/MAPK14 (a dominant-negative p38, dn-p38)...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28702871/expression-of-podoplanin-in-stromal-fibroblasts-plays-a-pivotal-role-in-the-prognosis-of-patients-with-pancreatic-cancer
#12
Kazuyoshi Hirayama, Hiroshi Kono, Yuuki Nakata, Yoshihiro Akazawa, Hiroyuki Wakana, Hisataka Fukushima, Hideki Fujii
PURPOSE: To investigate the role of podoplanin (PDPN) expression in invasive ductal carcinoma of the pancreas (IDCP) in humans. METHODS: Tumor samples were obtained from 95 patients with IDCP. Immunohistochemical staining was done to evaluate the expression of PDPN in cancer tissues. RESULTS: PDPN was detected predominantly in stromal fibroblasts, stained with α-smooth muscle actin. The cutoff value of PDPN-positive areas was calculated according to a histogram...
July 12, 2017: Surgery Today
https://www.readbyqxmd.com/read/28699239/analysis-of-individual-cells-identifies-cell-to-cell-variability-following-induction-of-cellular-senescence
#13
Christopher D Wiley, James M Flynn, Christapher Morrissey, Ronald Lebofsky, Joe Shuga, Xiao Dong, Marc A Unger, Jan Vijg, Simon Melov, Judith Campisi
Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single-cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall gene expression profile of senescent human fibroblast populations...
July 11, 2017: Aging Cell
https://www.readbyqxmd.com/read/28698228/perturbations-to-lysyl-oxidase-expression-broadly-influence-the-transcriptome-of-lung-fibroblasts
#14
Ivana Mižíková, Francesco Palumbo, Tamás Tábi, Susanne Herold, István Vadász, Konstantin Mayer, Werner Seeger, Rory E Morty
Lysyl oxidases are credited with pathogenic roles in lung diseases, including cancer, fibrosis, pulmonary hypertension, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). Lysyl oxidases facilitate the covalent intra- and inter-molecular cross-linking of collagen and elastin fibers, thereby imparting tensile strength to the extracellular matrix (ECM). Alternative ECM-independent roles have recently been proposed for lysyl oxidases, including regulation of growth factor signaling, chromatin remodeling, and transcriptional regulation; all of which impact cell phenotype...
July 10, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28697793/collagen-triple-helix-repeat-containing-1-negatively-regulated-by-microrna-30c-promotes-cell-proliferation-and-metastasis-and-indicates-poor-prognosis-in-breast-cancer
#15
Yuan-Hui Lai, Jian Chen, Xiao-Ping Wang, Yan-Qing Wu, Hai-Tao Peng, Xiao-Hong Lin, Wen-Jian Wang
BACKGROUND: Collagen triple helix repeat containing-1 (CTHRC1), which was firstly identified overexpressed in the adventitia and neointima of injured rat arteries, could inhibit collagen expression and increase cell migration. It was then found to be ubiquitously expressed in numerous cell types such as fibroblasts and smooth muscle cells, and aberrantly up-regulated in several malignant tumors. However, the functional role of CTHRC1 and its related mechanism in breast cancer still remains unclear...
July 12, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28696693/synthesis-and-evaluation-of-agelastatin-derivatives-as-potent-modulators-for-cancer-invasion-and-metastasis
#16
Alyssa Hope Antropow, Kun Xu, Rachel J Buchsbaum, Mohammad Movassaghi
The synthesis of new agelastatin alkaloid derivatives and their anticancer evaluation in the context of the breast cancer microenvironment is described. A variety of N1-alkyl and C5-ether agelastatin derivatives were accessed via application of our strategy for convergent imidazolone synthesis from a common thioester along with appropriately substituted urea and alcohol components. These agelastatin derivatives were evaluated in our three-dimensional co-culture assay for the effects of mammary fibroblasts on associated breast cancer cells...
July 11, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28695799/effect-of-human-hepatocellular-carcinoma-hepg2-cell-derived-exosome-on-the-differentiation-of-mesenchymal-stem-cells-and-their-interaction
#17
Fei Luo, Zhao Sun, Qin Han, Chunling Xue, Chunmei Bai
Objective To investigate the effect of human hepatocellular carcinoma HepG2 cell-derived Exosome on the differentiation of mesenchymal stem cells(MSC)into cancer-associated myofibroblasts(CAF)and the impacts of CAF on liver cancer cell proliferation,migration,and invasion. Methods The protein expression of HepG2 cell-derived Exosome was detected by Western blotting. MSCs were separated from human adipose tissue and cultured with HepG2 cell-derived Exosome(100 ng/nl)to initiate differentiation. The expressions of mesenchymal markers and several interleukins were also detected by Western blotting...
June 20, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28693293/mapk-inhibitors-enhance-cell-death-in-pyrogallol-treated-human-pulmonary-fibroblast-cells-via-increasing-o2-%C3%A2-levels
#18
Bo Ram Han, Woo Hyun Park
Pyrogallol (PG) induces apoptosis in lung cancer cells via the overproduction of O2(•-) and affects mitogen-activated protein kinases (MAPKs) in these cells. The aim of the present study was to elucidate the effect of PG and/or MAPK inhibitors on human pulmonary fibroblast (HPF) cell viability in relation to reactive oxygen species (ROS) and glutathione (GSH). Treatment with 50 or 100 µM PG inhibited the viability of HPF cells, and induced cell death and the loss of mitochondrial membrane potential (MMP; ΔΨm)...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693256/pirfenidone-may-revert-the-epithelial-to-mesenchymal-transition-in-human-lung-adenocarcinoma
#19
Ryota Kurimoto, Takahiro Ebata, Shunichiro Iwasawa, Tsukasa Ishiwata, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT-suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF-β. The present study aimed to determine whether pirfenidone has the potential to induce EMT-reversion, using nintedanib as a reference...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28693214/clustering-of-patients-with-intrahepatic-cholangiocarcinoma-based-on-serum-periostin-may-be-predictive-of-prognosis
#20
Chanitra Thuwajit, Peti Thuwajit, Pranisa Jamjantra, Chawalit Pairojkul, Sopit Wongkham, Vajarabhongsa Bhudhisawasdi, Junya Ono, Shoichiro Ohta, Kiminori Fujimoto, Kenji Izuhara
An effective serum biomarker may improve cholangiocarcinoma (CCA) management. Periostin (PN) has been demonstrated to be associated with aggressive CCA. The current study evaluated PN in blood serum for its diagnostic and prognostic potential in patients with CCA. Sera of 68 patients with CCA were collected prior to treatment, and PN levels were measured using an ELISA. Sera from 50 normal controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma and 21 with breast cancer were analyzed...
July 2017: Oncology Letters
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