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Cancer Associated Fibroblast Colon

Laura Pietrovito, Giuseppina Comito, Matteo Parri, Elisa Giannoni, Paola Chiarugi, Maria Letizia Taddei
BACKGROUND: The bisphosphonate Zoledronic acid (ZA) is a potent osteoclast inhibitor currently used in the clinic to reduce osteoporosis and cancer-induced osteolysis. Moreover, ZA exerts an anti-tumor effect in several tumors. Despite this evidence, the relevance of ZA in prostate cancer (PCa) is not completely understood. OBJECTIVE: To investigate the effect of ZA administration on the invasive properties of PC3 cells, which are characterised by RhoA-dependent amoeboid motility...
January 15, 2019: Current Cancer Drug Targets
Marta Ewelina Wawro, Katarzyna Chojnacka, Katarzyna Wieczorek-Szukała, Katarzyna Sobierajska, Jolanta Niewiarowska
Colon cancer, the second leading cause of cancer-related deaths in the world, is usually diagnosed in invasive stages. The interactions between cancer cells and cells located in their niche remain the crucial mechanism inducing tumor metastasis. The most important among those cells are cancer-associated fibroblasts (CAFs), the heterogeneous group of myofibroblasts transdifferentiated from numerous cells of different origin, including endothelium. The endothelial-to-mesenchymal transition (EndMT) is associated with modulation of cellular morphology, polarization and migration ability as a result of microtubule cytoskeleton reorganization...
December 23, 2018: International Journal of Molecular Sciences
Sho Takeda, Kunitoshi Shigeyasu, Yoshinaga Okugawa, Kazuhiro Yoshida, Yoshiko Mori, Shuya Yano, Kazuhiro Noma, Yuzo Umeda, Yoshitaka Kondo, Hiroyuki Kishimoto, Fuminori Teraishi, Takeshi Nagasaka, Hiroshi Tazawa, Shunsuke Kagawa, Toshiyoshi Fujiwara, Ajay Goel
Adenosine-to-inosine (A-to-I) RNA editing is a recently described epigenetic modification, which is believed to constitute a key oncogenic mechanism in human cancers. However, its functional role in cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) and its clinical significance remains unclear. Herein, we systematically analyzed a large cohort of 627 colorectal cancer (CRC) specimens, and investigated the expression pattern of ADAR1 and the its biological significance on the antizyme inhibitor 1 (AZIN1) RNA editing levels...
December 21, 2018: Cancer Letters
Dongyang Wang, Jianjun Zhang, Zengjun Li, Jianjun Han, Yongsheng Gao, Ming Chen, Yanqing Li
Fibroblast growth factor 19 (FGF19) promotes tumor growth in various types of cancer, but its function has not been investigated in the context of colorectal adenoma. Here, we report that FGF19 expression was greater in colorectal adenoma than in normal tissues, as measured by an enzyme-linked immunosorbent assay, quantitative reverse-transcription PCR and immunohistochemistry. FGF19 expression was also elevated in a subset of human colon cancer cell lines. Moreover, FGF receptor 4 (FGFR4), the cognate receptor for FGF19, was upregulated in colorectal adenoma tissues...
December 5, 2018: Digestive Diseases
Salem Majdop, Yehuda Skornick, Shmuel Avital, Liron Berkovich
Cancer-associated fibroblasts of the stroma play a major role in tumor promoting processes. In this study we evaluated the significance of Phospholipase D (PLD) enzyme activity in promoting human colon cancer malignant potency when interacting with proximal colonic fibroblasts. Human colon cancer cell lines SW480 and HCT116, and colonic fibroblasts CCD-18Co were used as an in vitro model. PLD's activity was measured in resting cancer cells and after culturing with fibroblasts and cancer-associated fibroblasts (CAFs) conditioned medium...
November 30, 2018: Cellular and Molecular Biology
Volker Ast, Theresa Kordaß, Marcus Oswald, Amol Kolte, David Eisel, Wolfram Osen, Stefan B Eichmüller, Alexander Berndt, Rainer König
Colorectal cancer remains a leading cause of cancer-related death worldwide. A previous transcriptomics based study characterized molecular subgroups of which the stromal subgroup was associated with the worst clinical outcome. Micro-RNAs (miRNAs) are well-known regulators of gene expression and can follow a non-linear repression mechanism. We set up a model combining piecewise linear and linear regression and applied this combined regression model to a comprehensive colon adenocarcinoma dataset. We identified miRNAs involved in regulating characteristic gene sets, particularly extracellular matrix remodeling in the stromal subgroup...
October 30, 2018: Oncotarget
Xiuying Li, Fengchang Huang, Xiaoyu Xu, Shuenqin Hu
Cancer-associated fibroblasts (CAFs) constitute a major component of the tumor microenvironment. CAFs regulated the growth and development, invasion and metastasis of primary tumors, as well as response to treatment. Recent studies indicated that monoclonal antibody therapies had limited success, thus more effective polyclonal antibodies (Poly Abs) is urgently needed. Poly Abs is a possible alternative because they target multiple antigens simultaneously. In this report, we prepared Poly Abs by immunizing rabbits with the bFGF-activated fibroblasts...
2018: International Journal of Biological Sciences
Cheng Peng, Xueqing Zou, Wanying Xia, Huijie Gao, Zequn Li, Naiqing Liu, Zongquan Xu, Chao Gao, Zhaobin He, Weibo Niu, Ruliang Fang, Siddhartha Biswas, Michael Agrez, Xuting Zhi, Jun Niu
Tumor microenvironment (TME) is the cellular environment in which tumor exists, and it contributes to tumor formation and progression. The TME is composed of tumor cells, stromal cells, cytokines, and chemotactic factors of which fibroblasts are the main cellular components. In our present study, we found that colorectal cancer (CRC) cells expressing integrin αvβ6 clearly could induce morphological changes in inactive fibroblasts and increased the expression of activated fibroblast markers such as alpha smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP)...
October 24, 2018: Bioscience Reports
Masashi Muramatsu, Shin Akakura, Lingqiu Gao, Jennifer Peresie, Benjamin Balderman, Irwin H Gelman
SSeCKS/Gravin/AKAP12 (SSeCKS) controls metastasis-associated PKC and Src signaling through direct scaffolding activity. SSeCKS is downregulated in the metastases of many human cancer types, and its forced re-expression suppresses the metastatic behavior of prostate cancer cells. SSeCKS is also downregulated in breast and prostate cancer stroma, and SSeCKS-null mice (KO) are metastasis-prone, suggesting a role in suppressing formation of the pre-metastatic niche. Here, we show that lung colonization and metastasis formation by B16F10 and SM1WT1[ Braf V600E ] mouse melanoma cells is 9-fold higher in syngeneic KO compared to WT hosts, although there is no difference in orthotopic tumor volumes...
September 11, 2018: Oncotarget
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
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
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
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
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
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
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
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
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
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
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
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