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https://www.readbyqxmd.com/read/29792311/pedf-regulates-plasticity-of-a-novel-lipid-mtoc-axis-in-prostate-cancer-associated-fibroblasts
#1
Francesca Nardi, Philip Fitchev, Omar E Franco, Jelena Ivanisevic, Adrian Scheibler, Simon W Hayward, Charles B Brendler, Michael A Welte, Susan E Crawford
Prostate tumors make metabolic adaptations to ensure adequate energy and amplify cell cycle regulators such as centrosomes to sustain their proliferative capacity. It is not known whether cancer associated fibroblasts (CAFs) undergo metabolic re-programming. We postulated that CAFs augment lipid storage and amplify centrosomal or non-centrosomal microtubule organizing centers (MTOCs) through a pigment epithelium-derived factor (PEDF)-dependent lipid-MTOC signaling axis. Primary normal human prostate fibroblasts (NFs) and CAFs were evaluated for lipid content, triacylglycerol-regulating proteins, MTOC number and distribution...
May 23, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29786795/protocols-for-studies-on-stromal-cells-in-prostate-cancer
#2
Damien A Leach, Grant Buchanan
Interactions between tumor cells and fibroblasts play a pivotal role in cancer development and progression. Indeed, the paracrine communication between these two cell types is known to have physiological effects that alter carcinogenic and metastatic potential. An often overlooked player in these interactions is the involvement of the extracellular matrix (ECM). The network of ECM proteins secreted from fibroblasts is reportedly altered with cancer initiation and progression, and in several cases has been associated with patient outcome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786108/mir%C3%A2-494-inhibits-cancer%C3%A2-initiating-cell-phenotypes-and-reverses-resistance-to-lapatinib-by-downregulating-fgfr2-in-her2%C3%A2-positive-gastric-cancer
#3
Yanxia Yu, Xuejuan Yu, Hong Liu, Qingxun Song, Yongmei Yang
In gastric cancer, >15% of cases are associated with the amplification of human epidermal growth factor receptor 2 (HER2), which leads to poor clinical outcomes. Lapatinib, a potent ATP‑competitive inhibitor, is a small, orally active molecule, which inhibits the tyrosine kinases of HER2 and epidermal growth factor receptor type 1. The activation of receptor tyrosine kinases can contribute to lapatinib resistance in HER2‑positive gastric cancer. The aim of the present study was to explore the effects of miR‑494 and FGFR2 in regulation of cancer‑initiating cell phenotypes and therapeutic efficiency of lapatinib in HER2‑positive gastric cancer...
May 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29785785/metabolism-within-the-tumor-microenvironment-and-its-implication-on-cancer-progression-an-ongoing-therapeutic-target
#4
REVIEW
Ma Carmen Ocaña, Beatriz Martínez-Poveda, Ana R Quesada, Miguel Ángel Medina
Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment (TME)...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29780673/breast-fibroblasts-in-both-cancer-and-normal-tissues-induce-phenotypic-transformation-of-breast-cancer-stem-cells-a-preliminary-study
#5
Bixiao Wang, Chunfang Xi, Mingwei Liu, Haichen Sun, Shuang Liu, Lei Song, Hua Kang
Background: Breast cancer stem cells (BCSCs) are associated with the invasion of breast cancer. In recent years, studies have demonstrated different phenotypes among BCSCs. Furthermore, BCSCs of diverse phenotypes are present at different tumour sites and different histological stages. Fibroblasts are involved in the phenotypic transformation of BCSCs. Cancer-associated fibroblasts (CAFs) participate in the induction of epithelial-mesenchymal transition, thereby promoting the acquisition of stem cell characteristics, but little is known about the role of normal fibroblasts (NFs) in the phenotypic transformation of BCSCs or about the effect of CAFs and NFs on BCSC phenotypes...
2018: PeerJ
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#6
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771943/cross-talk-between-human-airway-epithelial-cells-and-3t3-j2-feeder-cells-involves-partial-activation-of-human-met-by-murine-hgf
#7
Robert E Hynds, Kate H C Gowers, Ersilia Nigro, Colin R Butler, Paola Bonfanti, Adam Giangreco, Cecilia M Prêle, Sam M Janes
There is considerable interest in the ex vivo propagation of primary human basal epithelial stem/progenitor cells with a view to their use in drug development, toxicity testing and regenerative medicine. These cells can be expanded in co-culture with mitotically inactivated 3T3-J2 murine embryonic feeder cells but, similar to other epithelial cell culture systems employing 3T3-J2 cells, the aspects of cross-talk between 3T3-J2 cells and human airway basal cells that are critical for their expansion remain largely unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29769197/cancer-associated-fibroblasts-drive-glycolysis-in-a-targetable-signaling-loop-implicated-in-head-and-neck-squamous-cell-carcinoma-progression
#8
Dhruv Kumar, Jacob New, Vikalp Vishwakarma, Radhika Joshi, Jonathan Enders, Fangchen Lin, Sumana Dasari, Wade R Gutierrez, George Leef, Sivapriya Ponnurangam, Hemantkumar Chavan, Lydia Ganaden, Mackenzie M Thornton, Hongying Dai, Ossama Tawfik, Jeffrey Straub, Yelizaveta Shnayder, Kiran Kakarala, Terance Ted Tsue, Douglas A Girod, Bennett Van Houten, Shrikant Anant, Partha Krishnamurthy, Sufi Mary Thomas
Despite aggressive therapies, head and neck squamous cell carcinoma (HNSCC) is associated with a less than 50% 5-year survival rate. Late stage HNSCC frequently consists of up to 80% cancer-associated fibroblasts (CAF). We previously reported that CAF-secreted hepatocyte growth factor (HGF) facilitates HNSCC progression, however very little is known about the role of CAFs in HNSCC metabolism. Here we demonstrate that CAF-secreted HGF increases extracellular lactate levels in HNSCC via upregulation of glycolysis...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29765534/bi2536-induces-mitotic-catastrophe-and-radiosensitization-in-human-oral-cancer-cells
#9
Chieh-Yuan Cheng, Chung-Ji Liu, Yu-Chuen Huang, Shu-Hua Wu, Hsu-Wei Fang, Yu-Jen Chen
BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro ...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764866/lrrc15-is-a-novel-mesenchymal-protein-and-stromal-target-for-antibody-drug-conjugates
#10
James W Purcell, Sonia G Tanlimco, Jonathan A Hickson, Melvin Fox, Mien Sho, Lisa Durkin, Tamar Uziel, Rick Powers, Kelly D Foster-Duke, Thomas McGonigal, Subashri Kumar, Josue Samayoa, Dong Zhang, Joann P Palma, Sasmita Mishra, Diane Hollenbaugh, Kurt Gish, Susan E Morgan-Lappe, Eric D Hsi, Debra T Chao
Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29764588/-correlations-between-ape1-ref-1-icam-1-and-il-17a-levels-in-serum-and-radiation-pneumonitis-for-local-advanced-non-small-cell-lung-cancer-patients
#11
Leiming Guo, Gaofeng Ding, Wencai Xu, Hong Ge, Yue Jiang, Yufei Lu
BACKGROUND: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy...
May 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/29763934/inactivation-of-usp14-perturbs-ubiquitin-homeostasis-and-delays-the-cell-cycle-in-mouse-embryonic-fibroblasts-and-in-fruit-fly-drosophila
#12
Jung Hoon Lee, Seoyoung Park, Yejin Yun, Won Hoon Choi, Min-Ji Kang, Min Jae Lee
BACKGROUND/AIMS: The 26S proteasome is the key proteolytic complex for recognition and degradation of polyubiquitinated target substrates in eukaryotes. Among numerous proteasome-associated proteins, a deubiquitinating enzyme (DUB) USP14 has been identified as an endogenous inhibitor of the proteasome. Here, we explored the complex regulatory functions of USP14 that involve ubiquitin (Ub) homeostasis and substrate degradation in flies and mammals. METHODS: USP14-null primary and immortalized mouse embryonic fibroblasts (MEFs) and USP14 knocked-down Drosophila were analyzed in this study...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29762469/individualised-multimodal-treatment-strategies-for-anaplastic-and-poorly-differentiated-thyroid-cancer
#13
Sabine Wächter, Annette Wunderlich, Silvia Roth, Ioannis Mintziras, Elisabeth Maurer, Sebastian Hoffmann, Frederik A Verburg, Sebastian A Fellinger, Katharina Holzer, Detlef K Bartsch, Pietro Di Fazio
The prognosis of anaplastic (ATC) and poorly differentiated thyroid cancer (PDTC) is poor, due to their radioiodine refractoriness (RAI-R), high metastatic potential and current lack of effective treatment strategies. We aimed to examine the efficacy of the tyrosine kinase inhibitors (TKIs) sorafenib and selumetinib and the histone deacetylase inhibitor (HDACI) panobinostat in patient-derived tumor tissue (PDTT) of ATCs/PDTCs, the expression of sodium iodide symporter ( NIS ) and radioiodine up-take (RAI-U)...
May 15, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29760045/gfpt2-expressing-cancer-associated-fibroblasts-mediate-metabolic-reprogramming-in-human-lung-adenocarcinoma
#14
Weiruo Zhang, Gina Bouchard, Alice Yu, Majid Shafiq, Mehran Jamali, Joseph B Shrager, Kelsey Ayers, Shaimaa Bakr, Andrew J Gentles, Maximilian Diehn, Andrew Quon, Robert B West, Viswam Nair, Matt van de Rijn, Sandy Napel, Sylvia K Plevritis
Metabolic reprogramming of the tumor microenvironment is recognized as a cancer hallmark. To identify new molecular processes associated with tumor metabolism, we analyzed the transcriptome of bulk and flow-sorted human primary non-small cell lung cancer (NSCLC) together with 18FDG-positron emission tomography scans, which provide a clinical measure of glucose uptake. Tumors with higher glucose uptake were functionally enriched for molecular processes associated with invasion in adenocarcinoma (AD) and cell growth in squamous cell carcinoma (SCC)...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29758070/rapamycin-independent-igf2-expression-in-tsc2-null-mouse-embryo-fibroblasts-and-human-lymphangioleiomyomatosis-cells
#15
Blanca E Himes, Kseniya Obraztsova, Lurong Lian, Maya Shumyatcher, Ryan Rue, Elena N Atochina-Vasserman, Stella K Hur, Marisa S Bartolomei, Jilly F Evans, Vera P Krymskaya
Lymphangioleiomyomatosis (LAM) is a rare, almost exclusively female lung disease linked to inactivating mutations in tuberous sclerosis complex 2 (TSC2), a tumor suppressor gene that controls cell metabolic state and growth via regulation of the mechanistic target of rapamycin (mTORC1) signaling. mTORC1 is frequently activated in human cancers and, although the mTORC1 inhibitor rapamycin has a cytostatic effect, it is, in general, unable to elicit a robust curative effect or tumor regression. Using RNA-Seq, we identified (1) Insulin-like Growth Factor (IGF2) as one of the genes with the highest fold-change difference between human TSC2-null and TSC2-expressing angiomyolipoma cells from a patient with LAM, and (2) the mouse IGF2 homolog Igf2, as a top-ranking gene according to fold change between Tsc2-/- and Tsc2+/+ mouse embryo fibroblasts (MEFs)...
2018: PloS One
https://www.readbyqxmd.com/read/29756328/serum-derived-carcinoembryonic-antigen-cea-activates-fibroblasts-to-induce-a-local-re-modeling-of-the-extracellular-matrix-that-favors-the-engraftment-of-cea-expressing-tumor-cells
#16
Aws Abdul-Wahid, Marzena Cydzik, Nicholas W Fischer, Aaron Prodeus, John E Shively, Anne Martel, Samira Alminawi, Zeina Ghorab, Neil L Berinstein, Jean Gariépy
Elevated levels of the carcinoembryonic antigen (CEA; CEACAM5) in the serum of colorectal cancer (CRC) patients represent a clinical biomarker that correlates with disease recurrence. However, a mechanistic role for soluble CEA (sCEA) in tumor progression and metastasis remains to be established. In this study, we report that sCEA acts as a paracrine factor, activating human fibroblasts by signalling through both the STAT3 and AKT1-mTORC1 pathways, promoting their transition to a cancer-associated fibroblast (CaF) phenotype...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29753676/prostate-tumor-cell-exosomes-containing-hyaluronidase-hyal1-stimulate-prostate-stromal-cell-motility-by-engagement-of-fak-mediated-integrin-signaling
#17
Caitlin O McAtee, Christine Booth, Christian Elowsky, Lei Zhao, Jeremy Payne, Teresa Fangman, Steve Caplan, Michael D Henry, Melanie A Simpson
The hyaluronidase Hyal1 is clinically and functionally implicated in prostate cancer progression and metastasis. Elevated Hyal1 accelerates vesicular trafficking in prostate tumor cells, thereby enhancing their metastatic potential in an autocrine manner through increased motility and proliferation. In this report, we found Hyal1 protein is a component of exosomes produced by prostate tumor cell lines overexpressing Hyal1. We investigated the role of exosomally shed Hyal1 in modulating tumor cell autonomous functions and in modifying the behavior of prostate stromal cells...
May 10, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29753013/transferrin-anchored-poly-lactide-micelles-to-improve-anticancer-activity-of-curcumin-in-hepatic-and-cervical-cancer-cell-monolayers-and-3d-spheroids
#18
Preeti Kumari, Sri Vishnu Kiran Rompicharla, Omkara Swami Muddineti, Balaram Ghosh, Swati Biswas
In recent years, actively targeted drug delivery systems have been utilized in pre-clinical studies for site-specific delivery of drugs, which reduces toxicities associated with chemotherapy. This study reports the preparation of the tumor homing ligand, transferrin (Tf) anchored methoxy-polyethylene glycol-poly(d,l-lactide) polymeric micelles (Tf-PP). Curcumin which possess wide anti-cancer activity was loaded into the micelles. Tf-PPC with average particle size of 132.16 ± 1.3 nm and encapsulation efficiency of 88...
May 9, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29751106/curcumin-exerts-its-antitumor-effects-in-a-context-dependent-fashion
#19
Dominique Kreutz, Chomdao Sinthuvanich, Andrea Bileck, Lukas Janker, Besnik Muqaku, Astrid Slany, Christopher Gerner
Proteome profiling profoundly contributes to the understanding of cell response mechanisms to drug actions. Such knowledge may become a key to improve personalized medicine. In the present study, the effects of the natural remedy curcumin on breast cancer model systems were investigated. MCF-7, ZR-75-1 and TGF-β1 pretreated fibroblasts, mimicking cancer-associated fibroblasts (CAFs), were treated independently as well as in tumor cell/CAF co-cultures. Remarkably, co-culturing with CAF-like cells (CLCs) induced different proteome alterations in MCF-7 and ZR-75-1 cells, respectively...
May 8, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29749458/%C3%AE-klotho-inhibits-androgen-androgen-receptor%C3%A2-associated-epithelial%C3%A2-mesenchymal-transition-in-prostate-cancer-through-inactivation-of-erk1-2-signaling
#20
Zhao Liu, Hui Zhang, Sentai Ding, Shasha Qi, Shuai Liu, Dingqi Sun, Wei Dong, Lei Yin, Mingjiang Li, Xingbo Zhao, Jiaju Lu
The epithelial‑mesenchymal transition (EMT) is reported to have intimate crosstalk with androgen receptor (AR) signaling in prostate cancer (PCa) and is known to be responsible for castration resistance. Fibroblast growth factor/receptor (FGF/FGFR) signaling is also involved in tumor progression and EMT in multiple tissues. Several studies have investigated the role of βKlotho, an FGF/FGFR signaling co‑receptor in tumorigenesis. However, its role in PCa remains unknown. In the present study, the role of androgen in the EMT of PCa cells was examined by western blotting...
April 25, 2018: Oncology Reports
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