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Cancer Associated Fibroblast Colon

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https://www.readbyqxmd.com/read/30305726/tumor-cell-secreted-pld-increases-tumor-stemness-by-senescence-mediated-communication-with-microenvironment
#1
Sandra Muñoz-Galván, Antonio Lucena-Cacace, Marco Perez, Daniel Otero-Albiol, Julian Gomez-Cambronero, Amancio Carnero
Cancer cells are in continuous communication with the surrounding microenvironment and this communication can affect tumor evolution. In this work, we show that phospholipase D2 (PLD2) was overexpressed in colon tumors and is secreted by cancer cells, inducing senescence in neighboring fibroblasts. This occurs through its lipase domain. Senescence induced by its product, phosphatidic acid, leads to a senescence-associated secretory phenotype (SASP) able to increase the stem properties of cancer cells. This increase in stemness occurs by Wnt pathway activacion...
October 10, 2018: Oncogene
https://www.readbyqxmd.com/read/30304016/ovarian-stromal-cells-as-a-source-of-cancer-associated-fibroblasts-in-human-epithelial-ovarian-cancer-a-histopathological-study
#2
Masayoshi Fujisawa, Aye Moh-Moh-Aung, Zheng Zeng, Teizo Yoshimura, Yoji Wani, Akihiro Matsukawa
Fibroblasts are a major component of cancer tissue and known to contribute to cancer progression. However, it remains unknown whether they are derived from local fibroblasts or of other origin. This study was designed to identify the contribution of local stromal cells to cancer stroma in human epithelial ovarian cancer. Seventy-six cases of surgically resected primary ovarian carcinoma (48 cases confined to the ovaries and 28 cases with distant metastases) and 17 cases of secondary ovarian tumor (e.g. colon cancer metastasized to the ovary) were enrolled in this study...
2018: PloS One
https://www.readbyqxmd.com/read/30250018/endothelial-cell-activation-on-3d-matrices-derived-from-pdgf-bb-stimulated-fibroblasts-is-mediated-by-snail1
#3
Alberto Herrera, Mercedes Herrera, Natalia Guerra-Perez, Cristina Galindo-Pumariño, María Jesús Larriba, Vanesa García-Barberán, Beatriz Gil, Sara Giménez-Moyano, Reyes Ferreiro-Monteagudo, Pilar Veguillas, Antonio Candia, Raúl Peña, Jesús Pinto, Mª Laura García-Bermejo, Alberto Muñoz, Antonio García de Herreros, Félix Bonilla, Alfredo Carrato, Cristina Peña
Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant...
September 24, 2018: Oncogenesis
https://www.readbyqxmd.com/read/30246423/role-of-helicobacter-pylori-infection-in-cancer-associated-fibroblast-induced-epithelial-mesenchymal-transition-in-vitro
#4
Gracjana Krzysiek-Maczka, Aneta Targosz, Urszula Szczyrk, Malgorzata Strzałka, Zbigniew Sliwowski, Tomasz Brzozowski, Jarosław Czyz, Agata Ptak-Belowska
BACKGROUND: Major human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori-infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H...
September 23, 2018: Helicobacter
https://www.readbyqxmd.com/read/30177776/stem-cell-functionality-is-microenvironmentally-defined-during-tumour-expansion-and-therapy-response-in-colon-cancer
#5
Kristiaan J Lenos, Daniël M Miedema, Sophie C Lodestijn, Lisanne E Nijman, Tom van den Bosch, Xavier Romero Ros, Filipe C Lourenço, Maria C Lecca, Maartje van der Heijden, Sanne M van Neerven, Anita van Oort, Nicolas Leveille, Ronja S Adam, Felipe de Sousa E Melo, Joy Otten, Patrick Veerman, Guillaume Hypolite, Lianne Koens, Scott K Lyons, Giorgio Stassi, Douglas J Winton, Jan Paul Medema, Edward Morrissey, Maarten F Bijlsma, Louis Vermeulen
Solid malignancies have been speculated to depend on cancer stem cells (CSCs) for expansion and relapse after therapy. Here we report on quantitative analyses of lineage tracing data from primary colon cancer xenograft tissue to assess CSC functionality in a human solid malignancy. The temporally obtained clone size distribution data support a model in which stem cell function in established cancers is not intrinsically, but is entirely spatiotemporally orchestrated. Functional stem cells that drive tumour expansion predominantly reside at the tumour edge, close to cancer-associated fibroblasts...
October 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/30108164/increased-genetic-instability-and-accelerated-progression-of-colitis-associated-colorectal-cancer-through-intestinal-epithelium-specific-deletion-of-klf4
#6
Vincent W Yang, Yang Liu, Julie Kim, Kenneth R Shroyer, Agnieszka B Bialkowska
Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, regulates homeostasis of the intestinal epithelium. Previously, it was reported that KLF4 functions as a tumor suppressor in colorectal cancer. Here, evidence demonstrates that KLF4 mitigates the development and progression of colitis-associated colorectal cancer (CAC) in a murine model. Mice with intestinal epithelium-specific deletion of Klf4 ( Klf4ΔIS ) and control mice ( Klf4fl/fl ) were used to explore the role of KLF4 in the development of azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced CAC...
August 14, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/30101717/novel-tetrahydrobenzo-b-thiophene-compounds-exhibit-anticancer-activity-through-enhancing-apoptosis-and-inhibiting-tyrosine-kinase
#7
Souad A El-Metwally, Ali K Khalil, Abeer M El-Naggar, Wael M El-Sayed
ackground: Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. OBJECTIVE: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. METHODS: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7-tetrahydrobenzo[b] thiophene (1)...
August 13, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/30083271/carcinoma-associated-fibroblasts-promote-the-stemness-and-chemoresistance-of-colorectal-cancer-by-transferring-exosomal-lncrna-h19
#8
Jing Ren, Liang Ding, Dongya Zhang, Guoping Shi, Qianyun Xu, Sunan Shen, Yaping Wang, Tingting Wang, Yayi Hou
Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). The crosstalk between carcinoma- associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment promotes tumor development and confers chemoresistance. In this study, we further investigated the underlying tumor-promoting roles of CAFs and the molecular mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed...
2018: Theranostics
https://www.readbyqxmd.com/read/29981368/mechanisms-of-action-of-vitamin-d-in-colon-cancer
#9
REVIEW
Gemma Ferrer-Mayorga, María Jesús Larriba, Piero Crespo, Alberto Muñoz
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC...
July 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29907957/laminin-%C3%AE-1-orchestrates-vegfa-functions-in-the-ecosystem-of-colorectal-carcinoma
#10
Elmina Mammadova-Bach, Tristan Rupp, Caroline Spenlé, Ivo Jivkov, Pattabhiraman Shankaranarayanan, Annick Klein, Laura Pisarsky, Agnès Méchine-Neuville, Gérard Cremel, Michèle Kedinger, Olivier De Wever, Noona Ambartsumian, Sylvie Robine, Erwan Pencreach, Dominique Guenot, Patricia Simon-Assmann, Jacky G Goetz, Gertraud Orend, Olivier Lefebvre
BACKGROUND INFORMATION: Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. RESULTS: By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth...
June 15, 2018: Biology of the Cell
https://www.readbyqxmd.com/read/29901199/fibroblast-growth-factor-18-promotes-the-growth-migration-and-invasion-of-mda%C3%A2-mb%C3%A2-231-cells
#11
Ziyi Yu, Longquan Lou, Yi Zhao
Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein has been associated with poor overall survival in cancer patients. However, its function has not been investigated in breast cancer. In the present study, we demonstrated that FGF18 promoted cell growth and metastasis in vitro and stimulated tumor growth in xenograft models in vivo. FGF18 mediated the proliferation of MDA‑MB‑231 cells via the ERK/c‑Myc signaling pathway and induced epithelial‑to‑mesenchymal transition (EMT) factors to promote cancer migration and invasion...
August 2018: Oncology Reports
https://www.readbyqxmd.com/read/29899872/hitting-two-oncogenic-machineries-in-cancer-cells-cooperative-effects-of-the-multi-kinase-inhibitor-ponatinib-and-the-bet-bromodomain-blockers-jq1-or-dbet1-on-human-carcinoma-cells
#12
Karin Bauer, Daniela Berger, Christoph C Zielinski, Peter Valent, Thomas W Grunt
In recent years, numerous new targeted drugs, including multi-kinase inhibitors and epigenetic modulators have been developed for cancer treatment. Ponatinib blocks a variety of tyrosine kinases including ABL and fibroblast growth factor receptor (FGFR), and the BET bromodomain (BRD) antagonists JQ1 and dBET1 impede MYC oncogene expression. Both drugs have demonstrated substantial anti-cancer efficacy against several hematological malignancies. Solid tumors, on the other hand, although frequently driven by FGFR and/or MYC, are often unresponsive to these drugs...
May 29, 2018: Oncotarget
https://www.readbyqxmd.com/read/29888780/immunohistochemical-expression-of-fascin-1-in-colorectal-cancer-in-relation-to-clinical-and-pathological-parameters
#13
Barbara M Piskor, Anna Pryczynicz, Emilia Lubowicka, Katarzyna Miniewska, Justyna Zinczuk, Konrad Zareba, Katarzyna Guzinska-Ustymowicz
INTRODUCTION: Fascins are a group of proteins taking part in the maintenance of a proper structure of the cellular cytoskeleton. Fascin-1 is an actin-bundling protein present in neurons, fibroblasts, endothelial, smooth muscle, dendritic and mesenchymal cells whereas lack of its expression is characteristic of epithelial cells. Fascin-1 overexpression can be observed in neoplastic cells. Therefore, the aim of this study was to assess the expression of Fascin-1 protein in patients with colorectal cancer (CRC) and to analyze associations between Fascin-1 ex-pression and clinical-pathological parameters...
2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29885857/from-epidemiology-to-treatment-aspirin-s-prevention-of-brain-and-breast-cancer-and-cardioprotection-may-associate-with-its-metabolite-gentisic-acid
#14
Meric A Altinoz, Ilhan Elmaci, Salih Cengiz, Ebru Emekli-Alturfan, Aysel Ozpinar
BACKGROUND: Epidemiological studies indicate that aspirin consumption reduces the risk of tumors, which is especially relevant for colonic adenoma and carcinoma. Similar observations were made for glial brain tumors and breast cancers, yet the results are inconsistent. Gentisic acid (GA) is a minor catabolite of aspirin; yet humans carrying CYP2C9-variants incapable to catabolize aspirin to GA do not benefit from aspirin in prevention against colonic adenoma. GA blocks binding of Fibroblastic Growth Factor to its receptor and its sulphonate metabolite dobesilic acid blocks growth of C6 glioblastoma in vivo...
August 1, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29872392/gpcromics-gpcr-expression-in-cancer-cells-and-tumors-identifies-new-potential-biomarkers-and-therapeutic-targets
#15
Paul A Insel, Krishna Sriram, Shu Z Wiley, Andrea Wilderman, Trishna Katakia, Thalia McCann, Hiroshi Yokouchi, Lingzhi Zhang, Ross Corriden, Dongling Liu, Michael E Feigin, Randall P French, Andrew M Lowy, Fiona Murray
G protein-coupled receptors (GPCRs), the largest family of targets for approved drugs, are rarely targeted for cancer treatment, except for certain endocrine and hormone-responsive tumors. Limited knowledge regarding GPCR expression in cancer cells likely has contributed to this lack of use of GPCR-targeted drugs as cancer therapeutics. We thus undertook GPCRomic studies to define the expression of endoGPCRs (which respond to endogenous molecules such as hormones, neurotransmitters and metabolites) in multiple types of cancer cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29747061/serrated-epithelial-colorectal-polyps-hyperplastic-polyps-sessile-serrated-adenomas-with-perineurial-stroma-clinicopathological-and-molecular-analysis-of-a-new-series
#16
Katharina Erlenbach-Wünsch, Michel Bihl, Arndt Hartmann, Gabriel M Groisman, Michael Vieth, Abbas Agaimy
Serrated colorectal fibroblastic polyps (FPs) are rare benign mucosal lesions composed of serrated epithelial crypts separated and distorted by intimately associated bland spindle cell proliferations with perineurial-like phenotype. We herein describe 21 new FPs affecting 10 females and 9 males aged 45 to 80 yrs. (mean, 62 yrs). Lesions originated in the sigmoid colon/rectosigmoid junction (n = 16), rectum (n = 2), and other parts of the colon (n = 3). Most patients had additional synchronous or metachronous polyps: classical adenomas (12 patients), sessile serrated adenoma/SSA (1 patient), hyperplastic polyps/HPs (7 patients), both HPs and adenomas (6 patients) and colorectal cancer (2 patients)...
August 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29731961/macrophages-induce-budding-in-aggressive-human-colon-cancer-subtypes-by-protease-mediated-disruption-of-tight-junctions
#17
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720595/cytoglobin-affects-tumorigenesis-and-the-expression-of-ulcerative-colitis-associated-genes-under-chemically-induced-colitis-in-mice
#18
Mohammad Yassin, Hannelouise Kissow, Ben Vainer, Philomeena Daphne Joseph, Anders Hay-Schmidt, Jørgen Olsen, Anders Elm Pedersen
Cytoglobin (Cygb) is a member of the hemoglobin family and is thought to protect against cellular hypoxia and oxidative stress. These functions may be particularly important in inflammation-induced cancer, e.g., in patients with ulcerative colitis (UC). In this study, we investigated the development of inflammation and tumors in a murine model of inflammation-induced colorectal cancer using a combined treatment of azoxymethane and dextran sulfate sodium. A bioinformatics analysis of genome-wide expression data revealed increased colonic inflammation at the molecular level accompanied by enhanced macroscopic tumor development in Cygb-deficient mice...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29626120/a-tumor-imaging-method-targeting-cancer-associated-fibroblasts
#19
Anastasia Loktev, Thomas Lindner, Walter Mier, Jürgen Debus, Annette Altmann, Dirk Jäger, Frederik Giesel, Clemens Kratochwil, Philippe Barthe, Christian Roumestand, Uwe Haberkorn
The tumor stroma, which accounts for a large part of the tumor mass, represents an attractive target for the delivery of diagnostic and therapeutic compounds. Here, the focus is notably on a subpopulation of stromal cells, known as cancer-associated fibroblasts, which are present in more than 90% of epithelial carcinomas, including pancreatic, colon, and breast cancer. Cancer-associated fibroblasts feature high expression of fibroblast activation protein (FAP), which is not detectable in adult normal tissue but is associated with a poor prognosis in cancer patients...
September 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29560130/stromal-mir-20a-controls-paracrine-cxcl8-secretion-in-colitis-and-colon-cancer
#20
Steven A Signs, Robert C Fisher, Uyen Tran, Susmita Chakrabarti, Samaneh K Sarvestani, Shao Xiang, David Liska, Veronique Roche, Wei Lai, Haley R Gittleman, Oliver Wessely, Emina H Huang
Inflammatory bowel disease (IBD) affects one million people in the US. Ulcerative colitis (UC) is a subtype of IBD that can lead to colitis-associated cancer (CAC). In UC, the rate of CAC is 3-5-fold greater than the rate of sporadic colorectal cancer (CRC). The pathogenesis of UC and CAC are due to aberrant interactions between host immune system and microenvironment, but precise mechanisms are still unknown. In colitis and CAC, microenvironmental fibroblasts exhibit an activated, inflammatory phenotype that contributes to tumorigenesis accompanied by excessive secretion of the chemokine CXCL8...
February 27, 2018: Oncotarget
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