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Cancer associated fibroblast

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https://www.readbyqxmd.com/read/29346528/a-novel-stromal-lncrna-signature-reprograms-fibroblasts-to-promote-the-growth-of-oral-squamous-cell-carcinoma-via-lncrna-caf-interleukin-33
#1
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, Xiaofeng Huang, Qingang Hu, Hui Wang, Yuxian Song, Yanhong Ni, Yayi Hou
Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune cells in the tumor microenvironment (TME). CAFs interact with cancer cells to promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate cell growth, apoptosis, and metastasis of cancer cells, but their role in stromal cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29344235/metronomic-chemotherapy-remodel-cancer-associated-fibroblasts-to-decrease-chemoresistance-of-gastric-cancer-in-nude-mice
#2
Chao Wang, Wenqi Xi, Jinling Jiang, Jun Ji, Yingyan Yu, Zhenggang Zhu, Jun Zhang
The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu) chemotherapy with the metronomic pattern may cause significant chemoresistance compared with the traditional pattern, and whether CAFs are involved in drug resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and the mice were divided into five groups: The control group, intraperitoneally injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a week for 6 weeks...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29344186/downregulation-of-klotho-%C3%AE-is-associated-with-invasive-ductal-carcinoma-progression
#3
Ping Li, Meng Zhao, Xiaoli Qi, Xuegong Zhu, Jie Dai
Klotho β (KLB) is a single-pass transmembrane protein measuring 1,043 amino acids in length that shares 41.2% homology with klotho α (KLA). KLB is a co-receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4) pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor suppressor in human breast cancer; however, little is known regarding the role of KLB in breast cancer. In the present study, through an immunohistochemical analysis of invasive ductal carcinoma tissue arrays, low KLB expression was identified in invasive ductal carcinoma samples compared with paired adjacent non-tumorous breast tissues (82 cases)...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342254/distinctive-desmoplastic-3d-morphology-associated-with-brafv600e-in-papillary-thyroid-cancers
#4
M Tarabichi, A Antoniou, S Le Pennec, D Gacquer, N de Saint Aubain, L Craciun, T Cielen, I Laios, D Larsimont, G Andry, J E Dumont, C Maenhaut, V Detours
Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant (PTCV600E), the higher aggressiveness of these cancers is still debated. Objective: In PTCV600E we aimed to further characterize the extent of the stroma and its activation, the 3D tumor-stroma interface, and the proliferation rates of tumor and stromal fibroblasts. Design: We analyzed exomes, trancriptomes and images of 364 PTC from The Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTC for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary tumor blocks and 4 nodal metastases from one PTCV600E patient; and reconstructed the 3D volumes of one tumor and one metastatic blocks at histological resolution...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29339502/protein-aggregation-of-the-p63-transcription-factor-underlies-severe-skin-fragility-in-aec-syndrome
#5
Claudia Russo, Christian Osterburg, Anna Sirico, Dario Antonini, Raffaele Ambrosio, Julia Maren Würz, Jörg Rinnenthal, Marco Ferniani, Sebastian Kehrloesser, Birgit Schäfer, Peter Güntert, Satrajit Sinha, Volker Dötsch, Caterina Missero
The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29337182/human-pancreatic-tumor-organoids-reveal-loss-of-stem-cell-niche-factor-dependence-during-disease-progression
#6
Takashi Seino, Shintaro Kawasaki, Mariko Shimokawa, Hiroki Tamagawa, Kohta Toshimitsu, Masayuki Fujii, Yuki Ohta, Mami Matano, Kosaku Nanki, Kenta Kawasaki, Sirirat Takahashi, Shinya Sugimoto, Eisuke Iwasaki, Junichi Takagi, Takao Itoi, Minoru Kitago, Yuko Kitagawa, Takanori Kanai, Toshiro Sato
Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression signatures for specific subtypes, their functional differences remain elusive. Here, we established a pancreatic tumor organoid library encompassing 39 patient-derived PDACs and identified 3 functional subtypes based on their stem cell niche factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in the absence of Wnt and R-spondin...
January 10, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29337106/loss-of-tgf-%C3%AE-signaling-in-osteoblasts-increases-basic-fgf-and-promotes-prostate-cancer-bone-metastasis
#7
Xiangqi Meng, Alexandra Vander Ark, Paul Daft, Erica Woodford, Jie Wang, Zachary Madaj, Xiaohong Li
TGF-β plays a central role in prostate cancer (PCa) bone metastasis, and it is crucial to understand the bone cell-specific role of TGF-β signaling in this process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2 gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts (Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre KO mice, relative to their respective control Tgfbr2FloxE2 littermates...
January 11, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29335551/tumor-derived-exosomal-mir-1247-3p-induces-cancer-associated-fibroblast-activation-to-foster-lung-metastasis-of-liver-cancer
#8
Tian Fang, Hongwei Lv, Guishuai Lv, Ting Li, Changzheng Wang, Qin Han, Lexing Yu, Bo Su, Linna Guo, Shanna Huang, Dan Cao, Liang Tang, Shanhua Tang, Mengchao Wu, Wen Yang, Hongyang Wang
The communication between tumor-derived elements and stroma in the metastatic niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms tumor cells use to control metastatic niche formation are not fully understood. Here we report that in the lung metastatic niche, high-metastatic hepatocellular carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high-metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3, leading to activation of β1-integrin-NF-κB signaling in fibroblasts...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29334123/cancer-associated-fibroblasts-tailored-tumor-microenvironment-of-therapy-resistance-in-gastrointestinal-cancers
#9
REVIEW
Yeqi Sun, Ruifen Wang, Meng Qiao, Yanchun Xu, Wenbin Guan, Lifeng Wang
Gastrointestinal cancers (GI) are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis and also therapy resistance...
January 15, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29332341/association-of-the-combined-parameters-including-the-frequency-of-primary-cilia-cd8-tumor-infiltrating-lymphocytes-and-pd-1-expression-with-the-outcome-in-intestinal-cancer
#10
Josef Dvorak, Dimitar Hadzi Nikolov, Ladislav Dusek, Alzbeta Filipova, Igor Richter, David Buka, Ales Ryska, Jaroslav Mokry, Stanislav Filip, Bohuslav Melichar, Tomas Buchler, Jitka Abrahamova
PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the immune synapse. Microtubule structures, PC of cancer associated fibroblasts and immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and cancer cells, are regularly found in varying amounts in the microenvironment of solid tumors. The purpose of this study was to find out the potential association and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs in patients with intestinal cancer...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#11
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#12
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29325937/histopathological-analysis-of-tamoxifen-on-epidural-fibrosis
#13
Yasar Ozturk, Ismail Bozkurt, Mesut Emre Yaman, Yahya Guvenc, Tolga Tolunay, Deniz Billur, Fatma Kubra Erbay, Salim Senturk, Gokhan Bozkurt
BACKGROUND: Epidural fibrosis is a challenging topic in spinal surgery. This phenomenon constitutes one of the the main reasons behind "post-laminectomy syndrome" or "failed-back surgery syndrome", which leads to persistent back and leg pain in association with compression and/or stretching the nerve root or the dura. The exact mechanism of action in epidural fibrosis is complex and remains uncertain. Excessive deposition of collagen, fibronectin, and dermatan sulfate known as "extracellular matrix", and decrease of tissue cellularity results in epidural fibrosis...
January 8, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#14
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29325523/fanconi-anemia-with-sun-sensitivity-caused-by-a-xeroderma-pigmentosum-associated-missense-mutation-in-xpf
#15
Isabell Popp, Maqsood Punekar, Nick Telford, Stavros Stivaros, Kate Chandler, Meenakshi Minnis, Anna Castleton, Claire Higham, Louise Hopewell, D Gareth Evans, Anja Raams, Arjan F Theil, Stefan Meyer, Detlev Schindler
BACKGROUND: Fanconi anemia (FA) is an inherited genomic instability disorder with congenital and developmental abnormalities, bone marrow failure and predisposition to cancer early in life, and cellular sensitivity to DNA interstrand crosslinks. CASE PRESENTATION: A fifty-one-year old female patient, initially diagnosed with FA in childhood on the basis of classic features and increased chromosomal breakage, and remarkable sun-sensitivity is described. She only ever had mild haematological abnormalities and no history of malignancy...
January 11, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29323185/biogenesis-of-podosome-rosettes-through-fission
#16
Szu-Lin Kuo, Chien-Lin Chen, Yi-Ru Pan, Wen-Tai Chiu, Hong-Chen Chen
Podosomes are dynamic actin-based membrane protrusions that are important for extracellular matrix degradation and invasive cell motility. Individual podosomes are often found to organize into large rosette-like structures in some types of cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and certain highly invasive cancer cells. In this study, we show that new podosome rosettes arise through one of two mechanisms; de novo assembly or fission of a pre-existing podosome rosette in Src-transformed fibroblasts...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322415/laser-microdissection-of-cellular-compartments-for-expression-analyses-in-cancer-models
#17
Tae-Su Han, Masanobu Oshima
Cancer tissues are composed of various cell types including cancer cells, cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and endothelial cells. These surrounding stromal cells form the tumor microenvironment, partly through the inflammatory response, which plays an important role in the development and malignant progression of cancer. It is therefore important to examine the expression profiles and protein modifications of each cellular component independently to decipher the interaction between the tumor cells and the microenvironment...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29321666/are-there-multiple-cells-of-origin-of-merkel-cell-carcinoma
#18
REVIEW
J C Sunshine, N S Jahchan, J Sage, J Choi
Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29318551/analysis-of-invasive-activity-of-caf-spheroids-into-three-dimensional-3d-collagen-matrices
#19
María Ángeles Villaronga, Saúl Álvarez Teijeiro, Francisco Hermida-Prado, Marta Garzón-Arango, Victoria Sanz-Moreno, Juana María García-Pedrero
Tumor growth and progression is the result of a complex process controlled not only by malignant cancer cells but also by the surrounding tumor microenvironment (TME). Cancer associated fibroblasts (CAFs), the most abundant cellular component of TME, play an active role in tumor invasion and metastasis by promoting cancer cell invasion through cell-cell interactions and secretion of pro-invasive factors such as extracellular matrix (ECM)-degrading proteases. Due to their tumor-promoting activities, there is an emerging interest in investigating CAFs biology and its potential as drug targets for cancer therapies...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29317486/mutual-dependence-of-the-mrtf-srf-and-yap-tead-pathways-in-cancer-associated-fibroblasts-is-indirect-and-mediated-by-cytoskeletal-dynamics
#20
Charles T Foster, Francesco Gualdrini, Richard Treisman
Both the MRTF-SRF and the YAP-TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF-SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF-SRF and YAP-TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF-SRF genomic targets is also dependent on YAP-TEAD activity, and, conversely, YAP-TEAD target gene expression is also dependent on MRTF-SRF signaling...
January 9, 2018: Genes & Development
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