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Carcinoma-Associated Fibroblasts

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https://www.readbyqxmd.com/read/29137358/tm4sf5-promotes-metastatic-behavior-of-cells-in-3d-extracellular-matrix-gels-by-reducing-dependency-on-environmental-cues
#1
Dae-Geun Song, Gyu-Ho Lee, Seo Hee Nam, Jin-Gyu Cheong, Doyoung Jeong, Seo-Jin Lee, Cheol-Ho Pan, Jae Woo Jung, Hye-Jin Kim, Jihye Ryu, Ji Eon Kim, Somi Kim, Chang Yun Cho, Min-Kyung Kang, Kyung-Min Lee, Jung Weon Lee
Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma tissues and enhances migration in two-dimensional environments. Here, we investigated how TM4SF5 is involved in diverse pro-metastatic phenotypes in in vivo-like three-dimensional (3D) extracellular matrix gels. TM4SF5-positive cells aggressively formed invasive foci in 3D Matrigel, depending on TM4SF5-mediated signaling activity, cytoskeletal organization, and matrix metallopeptidase (MMP) 2-mediated extracellular remodeling, whereas TM4SF5-null cells did not...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136508/cancer-associated-fibroblasts-neutralize-the-anti-tumor-effect-of-csf1-receptor-blockade-by-inducing-pmn-mdsc-infiltration-of-tumors
#2
Vinit Kumar, Laxminarasimha Donthireddy, Douglas Marvel, Thomas Condamine, Fang Wang, Sergio Lavilla-Alonso, Ayumi Hashimoto, Prashanthi Vonteddu, Reeti Behera, Marlee A Goins, Charles Mulligan, Brian Nam, Neil Hockstein, Fred Denstman, Shanti Shakamuri, David W Speicher, Ashani T Weeraratna, Timothy Chao, Robert H Vonderheide, Lucia R Languino, Peter Ordentlich, Qin Liu, Xiaowei Xu, Albert Lo, Ellen Puré, Chunsheng Zhang, Andrey Loboda, Manuel A Sepulveda, Linda A Snyder, Dmitry I Gabrilovich
Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#3
Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29132723/ovarian-sex-cord-stromal-tumours-and-their-mimics
#4
REVIEW
Robert H Young
Sex cord-stromal tumours of the ovary include many of the most morphologically intriguing ovarian neoplasms and albeit many of them are rare, they factor into the differential diagnosis more often than their frequency might suggest. The most common malignant form, the adult granulosa cell tumour, may grossly simulate various surface epithelial neoplasms. Microscopically, confusion with endometrioid carcinoma may occur because the cords and microfollicles of the granulosa cell tumour may be mimicked by endometrioid carcinoma and the latter may have pale nuclei with nuclear grooves...
November 10, 2017: Pathology
https://www.readbyqxmd.com/read/29119969/tumor-targeting-efficacy-of-a-bf211-prodrug-through-hydrolysis-by-fibroblast-activation-protein-%C3%AE
#5
Xiao-Ping Chai, Guang-Long Sun, Yan-Fen Fang, Li-Hong Hu, Xuan Liu, Xiong-Wen Zhang
BF211, a bufalin (BF) derivative, exhibits stronger anti-cancer activity than BF but with potential cardiotoxicity. Fibroblast activation protein-α (FAPα) is a membrane-bound protease specifically expressed by carcinoma-associated fibroblasts, thus has been used for the selective delivery of anticancer agents. In this study, we used a FAPα-based prodrug strategy to synthesize a dipeptide (Z-Gly-Pro)-conjugated BF211 prodrug named BF211-03. BF211-03 was hydrolyzed by recombinant human FAPα (rhFAPα) and cleaved by homogenates of human colon cancer HCT-116 or human gastric cancer MGC-803 xenografts...
November 9, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29119003/novel-associations-of-bile-acid-diarrhoea-with-fatty-liver-disease-and-gallstones-a-cohort-retrospective-analysis
#6
Richard N Appleby, Jonathan D Nolan, Ian M Johnston, Sanjeev S Pattni, Jessica Fox, Julian Rf Walters
Background: Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods: A cohort of patients with chronic diarrhoea who underwent (75)selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29115573/fibroblast-activation-protein-%C3%AE-promotes-the-growth-and-migration-of-lung-cancer-cells-via-the-pi3k-and-sonic-hedgehog-pathways
#7
Jun Jia, Tracey A Martin, Lin Ye, Lin Meng, Nan Xia, Wen G Jiang, Xiaodong Zhang
A characteristic of the epithelial-to-mesenchymal transition in cancer cells is the upregulation of mesenchymal markers. Fibroblast activation protein α (FAPα) is predominantly expressed by stromal fibroblasts. Previous studies have demonstrated that FAPα is also expressed by certain epithelium-derived cancer cells and is involved in the regulation of certain signaling pathways. One of our previous studies showed that FAPα promoted the proliferation of breast cancer cells via the phosphatidylinositol-3-kinase (PI3K) signaling pathway...
October 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29115421/gene-expression-profiles-and-protein%C3%A2-protein-interaction-networks-during-tongue-carcinogenesis-in-the-tumor-microenvironment
#8
Wei Sun, Zeting Qiu, Wenqi Huang, Minghui Cao
Oral tongue squamous cell carcinoma (OTSCC) has a high incidence and is associated with a high mortality rate. Studies regarding the potential molecular mechanism of OTSCC in the tumor microenvironment (TME) are required. The present study aimed to perform bioinformatic analysis to identify important nodes, clusters and functional pathways during tongue carcinogenesis in the TME. After downloading the gene expression data of GSE42780, differentially expressed genes (DEGs) among carcinoma, dysplastic and normal samples in epithelia and fibroblasts were identified using the affy and limma packages with R version 3...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29100394/effects-of-photodynamic-therapy-on-dermal-fibroblasts-from-xeroderma-pigmentosum-and-gorlin-goltz-syndrome-patients
#9
Alicia Zamarrón, Marta García, Marcela Del Río, Fernando Larcher, Ángeles Juarranz
PDT is widely applied for the treatment of non-melanoma skin cancer pre-malignant and malignant lesions (actinic keratosis, basal cell carcinoma and in situ squamous cell carcinoma). In photodynamic therapy (PDT) the interaction of a photosensitizer (PS), light and oxygen leads to the formation of reactive oxygen species (ROS) and thus the selective tumor cells eradication. Xeroderma pigmentosum (XP) and Gorlin-Goltz Syndrome (GS) patients are at high risk of developing skin cancer in sun-exposed areas. Therefore, the use of PDT as a preventive treatment may constitute a very promising therapeutic modality for these syndromes...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100326/fiber-modified-hexon-chimeric-oncolytic-adenovirus-targeting-cancer-associated-fibroblasts-inhibits-tumor-growth-in-gastric-carcinoma
#10
Tao Pang, Xinghua Wang, Jun Gao, Wei Chen, Xiao Jun Shen, Ming Ming Nie, Tianhang Luo, Kai Yin, Guoen Fang, Kai Xuan Wang, Xu Chao Xue
Objective: To evaluate the effects of fiber-modified hexon-chimeric recombinant oncolytic adenovirus targeting cancer associated fibroblasts (CAFs) on the gastric CAFs and the transplantation tumor mice model of gastric carcinoma (GC). Results: Compared with BJ cells and GPFs, the reproduction and infectivity of P9, P9-4C or GP adenoviruses were markedly higher in gastric CAFs. In addition, P9, P9-4C or GP had a significantly relatively more killing effect on gastric CAFs compared with GPFs, and have less oncolytic effect in BJ cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29096734/endocrine-adiponectin-fgf15-19-axis-in-ethanol-induced-inflammation-and-alcoholic-liver-injury
#11
Min You, Zhou Zhou, Michael Daniels, Alvin Jogasuria
Alcoholic liver disease (ALD) is the most prevalent form of liver diseases, encompassing a spectrum of progressive pathological changes from steatosis to steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma. Alcoholic steatosis/steatohepatitis is the initial stage of ALD and a major risk factor for advanced liver injuries. Adiponectin is a hormone secreted from adipocytes. Fibroblast growth factor (FGF) 15 (human homolog, FGF19) is an ileum-derived hormone. Adipocyte-derived adiponectin and gut-derived FGF15/19 regulate each other, share common signaling cascades and exert similar beneficial functions...
November 2, 2017: Gene Expression
https://www.readbyqxmd.com/read/29071223/an-alignment-independent-3d-qsar-study-of-fgfr2-tyrosine-kinase-inhibitors
#12
Behzad Jafari, Maryam Hamzeh-Mivehroud, Ali Akbar Alizadeh, Mehdi Sharifi, Siavoush Dastmalchi
Purpose: Receptor tyrosine kinase (RTK) inhibitors are widely used pharmaceuticals in cancer therapy. Fibroblast growth factor receptors (FGFRs) are members of RTK superfamily which are highly expressed on the surface of carcinoma associate fibroblasts (CAFs). The involvement of FGFRs in different types of cancer makes them promising target in cancer therapy and hence, the identification of novel FGFR inhibitors is of great interest. In the current study we aimed to develop an alignment independent three dimensional quantitative structure-activity relationship (3D-QSAR) model for a set of 26 FGFR2 kinase inhibitors allowing the prediction of activity and identification of important structural features for these inhibitors...
September 2017: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29059160/il6-derived-from-cancer-associated-fibroblasts-promotes-chemoresistance-via-cxcr7-in-esophageal-squamous-cell-carcinoma
#13
Y Qiao, C Zhang, A Li, D Wang, Z Luo, Y Ping, B Zhou, S Liu, H Li, D Yue, Z Zhang, X Chen, Z Shen, J Lian, Y Li, S Wang, F Li, L Huang, L Wang, B Zhang, J Yu, Z Qin, Y Zhang
Various factors and cellular components in the tumor microenvironment are key drivers associated with drug resistance in many cancers. Here, we analyzed the factors and molecular mechanisms involved in chemoresistance in patients with esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6) derived mainly from cancer-associated fibroblasts played the most important role in chemoresistance by upregulating C-X-C motif chemokine receptor 7 (CXCR7) expression through signal transducer and activator of transcription 3/nuclear factor-κB pathway...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29052912/clinicopathologic-significance-of-rock2-expression-in-oral-squamous-cell-carcinomas
#14
Mauricio Rocha Dourado, Carine Ervolino de Oliveira, Iris Sawazaki-Calone, Elias Sundquist, Ricardo D Coletta, Tuula Salo
BACKGROUND: Rho-associated coiled-coil kinase 2 (ROCK2) is an oncoprotein that controls cytoskeleton organization and acts as prognostic marker in different types of solid tumors. ROCK2 overexpression is also observed in cancer-associated fibroblasts (CAF), which suggests its relevance within the tumor microenvironment. This study aimed to access the prognostic value of ROCK2 in oral squamous cell carcinomas (OSCC) and its association with CAF density. METHODS: ROCK2 immunohistochemical analysis was applied in 93 OSCC samples from 2 centers in Brazil and Finland...
October 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29039125/hypoxia-inducible-factor-hif-in-the-tumor-microenvironment-friend-or-foe
#15
REVIEW
Yanqing Huang, Daniel Lin, Cullen M Taniguchi
Hypoxia acts as an important regulator of physiological and pathological processes. Hypoxia inducible factors (HIFs) are the central players involved in the cellular adaptation to hypoxia and are regulated by oxygen sensing EGLN prolyl hydroxylases. Hypoxia affects many aspects of cellular growth through both redox effects and through the stabilization of HIFs. The HIF isoforms likely have differential effects on tumor growth via alteration of metabolism, growth, and self-renewal and are likely highly context-dependent...
October 13, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29030636/cancer-associated-fibroblasts-induce-metalloprotease-independent-cancer-cell-invasion-of-the-basement-membrane
#16
Alexandros Glentis, Philipp Oertle, Pascale Mariani, Aleksandra Chikina, Fatima El Marjou, Youmna Attieh, Francois Zaccarini, Marick Lae, Damarys Loew, Florent Dingli, Philemon Sirven, Marie Schoumacher, Basile G Gurchenkov, Marija Plodinec, Danijela Matic Vignjevic
At the stage of carcinoma in situ, the basement membrane (BM) segregates tumor cells from the stroma. This barrier must be breached to allow dissemination of the tumor cells to adjacent tissues. Cancer cells can perforate the BM using proteolysis; however, whether stromal cells play a role in this process remains unknown. Here we show that an abundant stromal cell population, cancer-associated fibroblasts (CAFs), promote cancer cell invasion through the BM. CAFs facilitate the breaching of the BM in a matrix metalloproteinase-independent manner...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29029799/interdependent-and-independent-multidimensional-role-of-tumor-microenvironment-on-hepatocellular-carcinoma
#17
REVIEW
Xue Wang, Waseem Hassan, Qaiser Jabeen, Ghulam Jilany Khan, Furqan Iqbal
The novelty of an effective therapeutic targeting for hepatocellular carcinoma (HCC) is based on improved understanding of each component of tumor microenvironment (TME) and its correspondent interactions at biological and molecular levels. In this context, new expansions for the treatment against TME and its communication with HCC are under exploration. Despite of the fact that blockage of growth factor receptors has become a treatment of choice in late phases of HCC in clinical practice, still a precise targeted treatment should address all the components of TME...
October 10, 2017: Cytokine
https://www.readbyqxmd.com/read/29029445/microrna-200c-increases-radiosensitivity-of-human-cancer-cells-with-activated-egfr-associated-signaling
#18
Taeryool Koo, Bong Jun Cho, Dan Hyo Kim, Ji Min Park, Eun Jung Choi, Hans H Kim, David J Lee, In Ah Kim
MicroRNA-200c (miR-200c) recently was found to have tumor-suppressive properties by inhibiting the epithelial-mesenchymal transition (EMT) in several cancers. miR-200c also interacts with various cellular signaling molecules and regulates many important signaling pathways. In this study, we investigated the radiosensitizing effect of miR-200c and its mechanism in a panel of human cancer cell lines. Malignant glioma (U251, T98G), breast cancer (MDA-MB-468), and lung carcinoma (A549) cells were transfected with control pre-microRNA, pre-miR-200c, or anti-miR-200c...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029429/twist1-is-highly-expressed-in-cancer-associated-fibroblasts-of-esophageal-squamous-cell-carcinoma-with-a-prognostic-significance
#19
So-Young Yeo, Sang-Yun Ha, Keun-Woo Lee, Yan Cui, Zhao-Ting Yang, Yan-Hua Xuan, Seok-Hyung Kim
Cancer-associated fibroblasts (CAFs) play important roles in cancer progression. Twist1 was recently reported to be a key regulator of CAFs in gastric cancer, but its role in other types of cancer remains unclear, especially for esophageal squamous cell carcinoma (ESCC). We assessed the Twist1 expression on stromal fibroblasts using immunohistochemistry in 169 tissue specimens from ESCC patients, and performed in vitro and in vivo experiments to confirm the role of Twist1 in CAFs of ESCC. And we investigated the biological pathways that are activated in Twist1-high ESCC using The Cancer Genome Atlas (TCGA) data...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029391/ginsenoside-rg3-inhibits-the-senescence-of-prostate-stromal-cells-through-down-regulation-of-interleukin-8-expression
#20
Yanfei Peng, Ran Zhang, Lingfei Kong, Yongmei Shen, Da Xu, Fang Zheng, Jianwei Liu, Qian Wu, Bona Jia, Ju Zhang
Senescent stromal cells support the development of prostate cancer and are considered potential therapeutic targets. This research evaluated the regulatory effects of ginsenoside Rg3 on the senescence of prostatic stromal cells pre-incubated in medium supplemented with 0.5% fetal bovine serum. The results revealed that ginsenoside Rg3 decreased the number of stromal cells positively stained with a senescent cell marker (senescence-associated β-galactosidase). Ginsenoside Rg3 also increased the viability of stromal cells and promoted cell cycle transition from G0/G1 to S phase, as well as inhibited the carcinoma-associated fibroblast-like phenotype in prostate stromal cells, through the up-regulation of smooth muscle cell markers SM22 and smooth muscle myosin heavy chain...
September 12, 2017: Oncotarget
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