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Cancer-associated fibroblasts

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https://www.readbyqxmd.com/read/28943953/six-low-penetrance-snps-for-the-estimation-of-breast-cancer-heritability-a-family-based-study-in-caucasian-italian-patients
#1
Simona De Summa, Francesca Graziano, Brunella Pilato, Rosamaria Pinto, Katia Danza, Rosanna Lacalamita, Simona Serratì, Domenico Sambiasi, Mario Grassi, Stefania Tommasi
Breast cancer is a malignancy with a strong heritable component. Genetic counseling has been principally focused on families carrying high-penetrance breast cancer 1/2, early onset genes. Current modeling suggests that the majority of the unexplained fraction of familial risk is likely to be explained by a polygenic model. The aim of the present study was to estimate the heritability (h(2)) of breast cancer susceptibility through the analysis of 6 single nucleotide polymorphisms (SNPs), nuclear mitotic apparatus protein 1, cyclin D1, cytochrome C oxidase copper chaperone, fibroblast growth factor receptor 2, TOX high mobility group box family member 3 and solute carrier family 4 member 7...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28942351/sphingosine-1-phosphate-and-cancer
#2
REVIEW
Nigel J Pyne, Ashref El Buri, David R Adams, Susan Pyne
The bioactive lipid, sphingosine 1-phosphate (S1P) is produced by phosphorylation of sphingosine and this is catalysed by two sphingosine kinase isoforms (SK1 and SK2). Here we discuss structural functional aspects of SK1 (which is a dimeric quaternary enzyme) that relate to coordinated coupling of membrane association with phosphorylation of Ser225 in the 'so-called' R-loop, catalytic activity and protein-protein interactions (e.g. TRAF2, PP2A and Gq). S1P formed by SK1 at the plasma-membrane is released from cells via S1P transporters to act on S1P receptors to promote tumorigenesis...
September 15, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28941173/the-influence-of-hyaluronic-acid-and-glioblastoma-cell-coculture-on-the-formation-of-endothelial-cell-networks-in-gelatin-hydrogels
#3
Mai T Ngo, Brendan A Harley
Glioblastoma (GBM) is the most common and deadly form of brain cancer. Interactions between GBM cells and vasculature in vivo contribute to poor clinical outcomes, with GBM-induced vessel co-option, regression, and subsequent angiogenesis strongly influencing GBM invasion. Here, elements of the GBM perivascular niche are incorporated into a methacrylamide-functionalized gelatin hydrogel as a means to examine GBM-vessel interactions. The complexity of 3D endothelial cell networks formed from human umbilical vein endothelial cells and normal human lung fibroblasts as a function of hydrogel properties and vascular endothelial growth factor (VEGF) presentation is presented...
September 22, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28940884/involvement-of-pdgf-ligands-and-receptors-in-tumorigenesis
#4
REVIEW
Carl-Henrik Heldin, Johan Lennartsson, Bengt Westermark
Platelet-derived growth factor (PDGF) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, over-activity of PDGF signaling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumors, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drives tumor cell proliferation and survival...
September 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28940685/the-antifibrotic-effects-of-pentoxifylline-improve-the-efficacy-of-gemcitabine-in-human-pancreatic-tumor-xenografts
#5
Jung Ho Kim, Byung Cheol Shin, Won Sang Park, Jaehwi Lee, Hyo-Jeong Kuh
We investigated the combinatorial effects of pentoxifylline (PTX) on the efficacy of gemcitabine (GEM) in a human pancreatic tumor xenograft model. PTX significantly improved the efficacy of GEM, as shown by a 50% reduction in tumor growth rate at 4 weeks of treatment compared with that in animals given GEM alone. The fluorescent drug doxorubicin (DOX) was used to test whether drug delivery was improved by PTX, contributing to the improved efficacy of GEM. PTX given for 2 weeks prior to DOX administration improved drug distribution by 1...
September 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28938000/podoplanin-increases-the-migration-of-human-fibroblasts-and-affects-the-endothelial-cell-network-formation-a-possible-role-for-cancer-associated-fibroblasts-in-breast-cancer-progression
#6
Jaroslaw Suchanski, Anna Tejchman, Maciej Zacharski, Aleksandra Piotrowska, Jedrzej Grzegrzolka, Grzegorz Chodaczek, Katarzyna Nowinska, Janusz Rys, Piotr Dziegiel, Claudine Kieda, Maciej Ugorski
In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28935175/cd61-and-caf-were-found-to-be-good-prognosis-factors-for-invasive-breast-cancer-patients
#7
Dongyan Cai, Xiaohong Wu, Tingting Hong, Yong Mao, Xiaosong Ge, Dong Hua
BACKGROUND: During the epithelial tumor development process, changes in tumor cell genes are an important driving factor for tumorigenesis. Recently, however, studies have shown that the tumor microenvironment, especially for cancer-associated fibroblasts (CAFs) and the infiltration of platelets into tumors, plays an essential role in the progression of human malignant disease. METHODS: In this study, we investigated the presence and prognostic role of podoplanin-expressing CAFs (CAF+), the infiltration of platelets into tumors (CD61+) and platelet count before surgery in a large sample of patients with breast cancer...
June 30, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28934847/participation-of-ccl1-in-snail-positive-fibroblasts-in-colorectal-cancer-contribute-to-5-fluorouracil-paclitaxel-chemoresistance
#8
Ziqian Li, Kaying Chan, Yifei Qi, Linlin Lu, Fen Ning, Mengling Wu, Yuan Wang, Shaohui Cai, Jun Du
Purpose: Cancer-associated fibroblasts (CAFs) activated by cancer cells has a central role in development and malignant biological behavior in colorectal cancer (CRC). Adult fibroblasts do not express Snail, but Snail-positive fibroblasts are discovered in the stroma of malignant CRC and reported to be the key role to chemoresistance. However, the reciprocal effect of CAFs expressed Snail to chemoresistance on CRC cells and the underlying molecular mechanisms are not fully characterized...
September 18, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28934010/down-regulation-of-klf5-in-cancer-associated-fibroblasts-inhibit-gastric-cancer-cells-progression-by-ccl5-ccr5-axis
#9
Tingsong Yang, Min Chen, Yingying Sun, Xiaobing Zhang, Zhou Zhang, Bin Xu, Jie Hua, Zhigang He, Zhenshun Song
It was well known that cancer-associated fibroblasts (CAFs) were an essential factor in tumor progression. However, the actual mechanism of stromal fibroblasts activation and tumor promoting effects remain unclear. Here, we showed that KLF5 expression was more frequently observed in gastric cancer-associated fibroblasts compared with normal mucosal fibroblasts. Moreover, KLF5 expression in tumor stroma was closely associated with clinicopathological features such as tumor size, invasion depth, cell grade and lymph node metastasis, as well as poor prognosis in patients with gastric cancer...
September 21, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28933766/involvement-of-the-integrin-%C3%AE-1%C3%AE-1-in-the-progression-of-colorectal-cancer
#10
Salah Boudjadi, Gérald Bernatchez, Blanche Sénicourt, Marco Beauséjour, Pierre H Vachon, Julie C Carrier, Jean-François Beaulieu
Integrins are a family of heterodimeric glycoproteins involved in bidirectional cell signaling that participate in the regulation of cell shape, adhesion, migration, survival and proliferation. The integrin α1β1 is known to be involved in RAS/ERK proliferative pathway activation and plays an important role in fibroblast proliferation. In the small intestine, the integrin α1 subunit is present in the crypt proliferative compartment and absent in the villus. We have recently shown that the integrin α1 protein and transcript (ITGA1) are present in a large proportion of colorectal cancers (CRC) and that their expression is controlled by the MYC oncogenic factor...
July 26, 2017: Cancers
https://www.readbyqxmd.com/read/28931560/ret-mediated-modulation-of-tumour-microenvironment-and-immune-response-in-men2
#11
Maria Domenica Castellone, Rosa Marina Melillo
Medullary thyroid carcinomas (MTC) arise from thyroid parafollicular, calcitonin-producing C-cells and can occur either as sporadic or as hereditary diseases in the context of familial syndromes, including multiple endocrine neoplasia 2A (MEN2A), multiple endocrine neoplasia 2B (MEN2B) and familial MTC (FMTC). In a large fraction of sporadic cases, and virtually in all inherited cases of MTC, activating point mutations of the RET proto-oncogene are found. RET encodes for a receptor tyrosine kinase protein endowed with transforming potential on thyroid parafollicular cells...
September 20, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28931556/cancer-associated-fibroblasts-lead-tumor-invasion-through-integrin-%C3%AE-3-dependent-fibronectin-assembly
#12
Youmna Attieh, Andrew G Clark, Carina Grass, Sophie Richon, Marc Pocard, Pascale Mariani, Nadia Elkhatib, Timo Betz, Basile Gurchenkov, Danijela Matic Vignjevic
Cancer-associated fibroblasts (CAFs) are the most abundant cells of the tumor stroma. Their capacity to contract the matrix and induce invasion of cancer cells has been well documented. However, it is not clear whether CAFs remodel the matrix by other means, such as degradation, matrix deposition, or stiffening. We now show that CAFs assemble fibronectin (FN) and trigger invasion mainly via integrin-αvβ3. In the absence of FN, contractility of the matrix by CAFs is preserved, but their ability to induce invasion is abrogated...
September 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28930154/autophagy-and-inflammatory-response-in-the-tumor-microenvironment
#13
REVIEW
Daniel Ngabire, Gun-Do Kim
Cell death is the last fate of the life cycle of cells. Different pathways involved in cell death are known to date, and are mostly represented by apoptosis, necrosis, and autophagy. Autophagy is one of the most preserved cell death pathways, characterized by the elimination of large parts of cytoplasmic components after being consumed by a double-membraned vesicle called an autophagosome. The formed autophagosome then fuses with a lysosome containing degrading enzymes and leads to the digestion of the autophagosome content...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28927692/prognostic-influence-of-tumor-stroma-on-breast-cancer-subtypes
#14
Sandra Cid, Noemi Eiro, Berta Fernández, Rosario Sánchez, Alejandro Andicoechea, Pablo Ignacio Fernández-Muñiz, Luis O González, Francisco J Vizoso
INTRODUCTION: The objective of the present work was to evaluate the impact of the phenotype of both intratumoral mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs), assessed as to their expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) on prognosis in different breast cancer subtypes. MATERIALS AND METHODS: A total of 247 tumors of patients with primary ductal invasive breast cancer were categorized into 1 of 4 major subtypes, using the 3 standard immunohistochemical markers (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor/Neu 2 [HER2] receptor status)...
August 19, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28927152/expression-levels-of-fgfr3-as-a-prognostic-marker-for-the-progression-of-primary-pt1-bladder-cancer-and-its-association-with-mutation-status
#15
Ho Won Kang, Ye-Hwan Kim, Pildu Jeong, Cheol Park, Won Tae Kim, Dong Hee Ryu, Eun-Jong Cha, Yun-Sok Ha, Tae-Hwan Kim, Tae Gyun Kwon, Sung-Kwon Moon, Yung Hyun Choi, Seok-Joong Yun, Wun-Jae Kim
The present study examined the utility of fibroblast growth factor receptor 3 (FGFR3) mutation status and gene expression as a prognostic marker in primary pT1 bladder cancer (BC). A total of 120 patients with primary pT1 BC were enrolled. FGFR3 mutation status was determined by direct sequencing and FGFR3 mRNA expression level was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The results were compared with the clinicopathological parameters, and the prognostic value of FGFR3 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression test...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927027/cancer-associated-fibroblasts-an-essential-role-in-the-tumor-microenvironment
#16
Leilei Tao, Guichun Huang, Haizhu Song, Yitian Chen, Longbang Chen
Fibroblasts in the tumor stroma are well recognized as having an indispensable role in carcinogenesis, including in the initiation of epithelial tumor formation. The association between cancer cells and fibroblasts has been highlighted in several previous studies. Regulation factors released from cancer-associated fibroblasts (CAFs) into the tumor microenvironment have essential roles, including the support of tumor growth, angiogenesis, metastasis and therapy resistance. A mutual interaction between tumor-induced fibroblast activation, and fibroblast-induced tumor proliferation and metastasis occurs, thus CAFs act as tumor supporters...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926101/the-metabolic-cross-talk-between-epithelial-cancer-cells-and-stromal-fibroblasts-in-ovarian-cancer-progression-autophagy-plays-a-role
#17
REVIEW
Chanitra Thuwajit, Alessandra Ferraresi, Rossella Titone, Peti Thuwajit, Ciro Isidoro
Cancer and stromal cells, which include (cancer-associated) fibroblasts, adipocytes, and immune cells, constitute a mixed cellular ecosystem that dynamically influences the behavior of each component, creating conditions that ultimately favor the emergence of malignant clones. Ovarian cancer cells release cytokines that recruit and activate stromal fibroblasts and immune cells, so perpetuating a state of inflammation in the stroma that hampers the immune response and facilitates cancer survival and propagation...
September 19, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28923947/tpc2-polymorphisms-associated-with-a-hair-pigmentation-phenotype-in-humans-result-in-gain-of-channel-function-by-independent-mechanisms
#18
Yu-Kai Chao, Verena Schludi, Cheng-Chang Chen, Elisabeth Butz, O N Phuong Nguyen, Martin Müller, Jens Krüger, Claudia Kammerbauer, Manu Ben-Johny, Angelika M Vollmar, Carola Berking, Martin Biel, Christian A Wahl-Schott, Christian Grimm
Two-pore channels (TPCs) are endolysosomal cation channels. Two members exist in humans, TPC1 and TPC2. Functional roles associated with the ubiquitously expressed TPCs include VEGF-induced neoangiogenesis, LDL-cholesterol trafficking and degradation, physical endurance under fasting conditions, autophagy regulation, the acrosome reaction in sperm, cancer cell migration, and intracellular trafficking of pathogens such as Ebola virus or bacterial toxins (e.g., cholera toxin). In a genome-wide association study for variants associated with human pigmentation characteristics two coding variants of TPC2, rs35264875 (encoding M484L) and rs3829241 (encoding G734E), have been found to be associated with a shift from brown to blond hair color...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28922783/targeted-therapy-for-cancer-associated-fibroblasts-are-we-there-yet
#19
Reagan M Barnett, Eduardo Vilar
No abstract text is available yet for this article.
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922779/targeting-the-myofibroblastic-cancer-associated-fibroblast-phenotype-through-inhibition-of-nox4
#20
Christopher J Hanley, Massimiliano Mellone, Kirsty Ford, Steve M Thirdborough, Toby Mellows, Steven J Frampton, David M Smith, Elena Harden, Cedric Szyndralewiez, Marc Bullock, Fergus Noble, Karwan A Moutasim, Emma V King, Pandurangan Vijayanand, Alex H Mirnezami, Timothy J Underwood, Christian H Ottensmeier, Gareth J Thomas
Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry...
January 1, 2018: Journal of the National Cancer Institute
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