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https://www.readbyqxmd.com/read/29141020/genomic-analysis-of-atypical-fibroxanthoma
#1
Kevin Lai, Catherine A Harwood, Karin J Purdie, Charlotte M Proby, Irene M Leigh, Namita Ravi, Thaddeus W Mully, Lionel Brooks, Priscilla M Sandoval, Michael D Rosenblum, Sarah T Arron
Atypical fibroxanthoma (AFX), is a rare type of skin cancer affecting older individuals with sun damaged skin. Since there is limited genomic information about AFX, our study seeks to improve the understanding of AFX through whole-exome and RNA sequencing of 8 matched tumor-normal samples. AFX is a highly mutated malignancy with recurrent mutations in a number of genes, including COL11A1, ERBB4, CSMD3, and FAT1. The majority of mutations identified were UV signature (C>T in dipyrimidines). We observed deletion of chromosomal segments on chr9p and chr13q, including tumor suppressor genes such as KANK1 and CDKN2A, but no gene fusions were found...
2017: PloS One
https://www.readbyqxmd.com/read/29137396/tgfbr-idh1-cav1-axis-promotes-tgf-%C3%AE-signalling-in-cancer-associated-fibroblast
#2
Xiaodan Hou, Jieying Zhang, Yongbin Wang, Wujun Xiong, Jun Mi
TGF-β signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- β signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-β signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of α-ketoglutarate (α-KG) by accelerating glutamine metabolization. Interestingly, α-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137358/tm4sf5-promotes-metastatic-behavior-of-cells-in-3d-extracellular-matrix-gels-by-reducing-dependency-on-environmental-cues
#3
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/29137220/stromal-cyclin-d1-promotes-heterotypic-immune-signaling-and-breast-cancer-growth
#4
Timothy G Pestell, Xuanmao Jiao, Mukesh Kumar, Amy R Peck, Marco Prisco, Shengqiong Deng, Zhiping Li, Adam Ertel, Mathew C Casimiro, Xiaoming Ju, Agnese Di Rocco, Gabriele Di Sante, Sanjay Katiyar, Alison Shupp, Michael P Lisanti, Pooja Jain, Kongming Wu, Hallgeir Rui, Douglas C Hooper, Zuoren Yu, Aaron R Goldman, David W Speicher, Lisa Laury-Kleintop, Richard G Pestell
The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that drives cell autonomous cell cycle progression and proliferation. Herein we show cyclin D1 abundance is increased >30-fold in the stromal fibroblasts of patients with invasive breast cancer, associated with poor outcome. Cyclin D1 transformed hTERT human fibroblast to a cancer-associated fibroblast phenotype. Stromal fibroblast expression of cyclin D1 (cyclin D1(Stroma)) in vivo, enhanced breast epithelial cancer tumor growth, restrained apoptosis, and increased autophagy...
October 10, 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
#5
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/29136500/does-csf1r-blockade-turn-into-friendly-fire
#6
Tim F Greten
In this issue of Cancer Cell, Kumar et al. describe how CSF1R blockade induces not only an expected deprivation of tumor-associated macrophages, but also an accumulation of tumor-infiltrating polymorphonuclear mononuclear cells caused by Cxcl-1 released from cancer-associated fibroblasts.
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29135454/expression-of-a-novel-cnpy2-isoform-in-colorectal-cancer-and-its-association-with-oncologic-prognosis
#7
Jianhong Peng, Qingjian Ou, Jian Guo, Zhizhong Pan, Rongxin Zhang, Xiaojun Wu, Yujie Zhao, Yuxiang Deng, Caixia Li, Fulong Wang, Liren Li, Gong Chen, Zhenhai Lu, Peirong Ding, Desen Wan, Yujing Fang
Colorectal cancer (CRC) is a leading cause of cancer-related mortality. Recently, we identified a novel biomarker, canopy fibroblast growth factor signaling regulator 2 (CNPY2) isoform2, and subsequently investigated its expression and prognostic value in CRC patients. We initially generated CNPY2 isoform2 monoclonal antibodies and examined CNPY2 isoform2 expression in CRC cell lines and tissues using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry analyses. We found that CNPY2 isoform2 expression significantly increased in tumor cell lines and tissues compared with that in normal colon epithelial cells and tumor-adjacent normal tissues...
November 13, 2017: Aging
https://www.readbyqxmd.com/read/29134439/treatment-related-survival-associations-of-claudin-2-expression-in-fibroblasts-of-colorectal-cancer
#8
Artur Mezheyeuski, Carina Strell, Ina Hrynchyk, Tormod Kyrre Guren, Anca Dragomir, Tatyana Doroshenko, Oksana Pashkova, Julia Gorgun, Kseniya Ruksha, Per Pfeiffer, Elin H Kure, Halfdan Sorbye, David Edler, Anna Martling, Bengt Glimelius, Arne Östman, Anna Portyanko
Claudin-2 is a trans-membrane protein-component of tight junctions in epithelial cells. Elevated claudin-2 expression has been reported in colorectal cancer (CRC). The aim of this study was to investigate the expression patterns of claudin-2 in human CRC samples and analyze its association with clinical characteristics and treatment outcome. TMAs of primary tumors from two cohorts of metastatic CRC (mCRC) were used. Claudin-2 IHC staining was evaluated in a semi-quantitative manner in different regions and cell types...
November 13, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#9
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/29122677/inducible-knockdown-of-procollagen-i-protects-mice-from-liver-fibrosis-and-leads-to-dysregulated-matrix-genes-and-attenuated-inflammation
#10
Olena Molokanova, Kai Schönig, Shih-Yen Weng, Xiaoyu Wang, Matthias Bros, Mustafa Diken, Svetlana Ohngemach, Morten Karsdal, Dennis Strand, Alexei Nikolaev, Leonid Eshkind, Detlef Schuppan
Organ fibrosis is characterized by a chronic wound-healing response, with excess deposition of extracellular matrix components. Here, collagen type I represents the most abundant scar component and a primary target for antifibrotic therapies. Liver fibrosis can progress to cirrhosis and primary liver cancer, which are the major causes of liver related morbidity and mortality. However, a (pro-)collagen type I specific therapy remains difficult and its therapeutic abrogation may incur unwanted side effects. We therefore designed tetracycline-regulated procollagen alpha1(I) short hairpin (sh)RNA expressing mice that permit a highly efficient inducible knockdown of the procollagen alpha1(I) gene in activated (myo-)fibroblasts, to study the effect of induced procollagen type I deficiency...
November 6, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29119969/tumor-targeting-efficacy-of-a-bf211-prodrug-through-hydrolysis-by-fibroblast-activation-protein-%C3%AE
#11
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/29116739/gold-nanocluster-mediated-cellular-death-under-electromagnetic-radiation
#12
Anna Cifuentes-Rius, Angela Ivask, Shreya Das, Nuria Penya Auladell, Laura Fabregas, Nicholas L Fletcher, Zachary H Houston, Kristofer James Thurecht, Nicolas H Voelcker
Gold nanoclusters (Au NCs) have become a promising nanomaterial for cancer therapy due to their biocompatibility and fluorescent properties. In this study, the effect of ultrasmall protein-stabilized 2 nm Au NCs on six types of mammalian cells (fibroblasts, B-lymphocytes, glioblastoma, neuroblastoma, and two types of prostate cancer cells) under electromagnetic radiation is investigated. Cellular association of Au NCs in vitro is concentration-dependent and Au NCs have low intrinsic toxicity. However, when Au NC-incubated cells are exposed to 1 GHz electromagnetic field (microwave radiation, µW), cell viability significantly decreases thus demonstrating that Au NCs exhibit specific µW dependent cytotoxicity, likely resulting from localized heating...
November 8, 2017: ACS Applied Materials & Interfaces
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
#13
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/29112233/neuroendocrine-tumors-and-fibrosis-an-unsolved-mystery
#14
REVIEW
Faidon-Marios Laskaratos, Krista Rombouts, Martyn Caplin, Christos Toumpanakis, Christina Thirlwell, Dalvinder Mandair
Neuroendocrine tumors are a heterogeneous group of slow-growing neoplasms arising mainly from the enterochromaffin cells of the digestive and respiratory tract. Although they are relatively rare, their incidence is rising. It has long been observed that they often are associated with the development of fibrosis, both local and distant. Fibrotic complications, such as carcinoid heart disease and mesenteric desmoplasia, may lead to considerable morbidity or even affect prognosis. The elucidation of the pathophysiology of fibrosis would be of critical importance for the development of targeted therapeutic strategies...
November 7, 2017: Cancer
https://www.readbyqxmd.com/read/29112161/collateral-damage-intended-cancer-associated-fibroblasts-and-vasculature-are-potential-targets-in-cancer-therapy
#15
REVIEW
Ana Cavaco, Maryam Rezaei, Stephan Niland, Johannes A Eble
After oncogenic transformation, tumor cells rewire their metabolism to obtain sufficient energy and biochemical building blocks for cell proliferation, even under hypoxic conditions. Glucose and glutamine become their major limiting nutritional demands. Instead of being autonomous, tumor cells change their immediate environment not only by their metabolites but also by mediators, such as juxtacrine cell contacts, chemokines and other cytokines. Thus, the tumor cells shape their microenvironment as well as induce resident cells, such as fibroblasts and endothelial cells (ECs), to support them...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29112159/mir-1224-5p-mediates-mitochondrial-damage-to-affect-silica-induced-pulmonary-fibrosis-by-targeting-becn1
#16
Qiuyun Wu, Tiantian Xu, Yi Liu, Yan Li, Jiali Yuan, Wenxi Yao, Qi Xu, Weiwen Yan, Chunhui Ni
Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1...
November 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29110840/immunohistochemical-and-genetic-characteristics-of-lung-cancer-mimicking-organizing-pneumonia
#17
Tomohiro Ichikawa, Koichi Saruwatari, Sachiyo Mimaki, Masato Sugano, Keiju Aokage, Motohiro Kojima, Tomoyuki Hishida, Satoshi Fujii, Junji Yoshida, Takeshi Kuwata, Atsushi Ochiai, Kenji Suzuki, Masahiro Tsuboi, Koichi Goto, Katsuya Tsuchihara, Genichiro Ishii
INTRODUCTION: Lung cancer mimicking organizing pneumonia (LCOP) is a novel radiological entity of lung adenocarcinoma that could be misdiagnosed as inflammatory lesions. However, the characteristic biological and genetic features of LCOP are not fully clarified. MATERIALS AND METHODS: We used thin-section CT images to select cases of (LCOP) among surgically resected lung adenocarcinoma patients. We compared the clinicopathological characteristics and the immunophenotypes of LCOP (n=44) and other lepidic-predominant adenocarcinomas (non-LCOP, n=56)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29109792/mir-205-yap1-in-activated-fibroblasts-of-breast-tumor-promotes-vegf-independent-angiogenesis-through-stat3-signaling
#18
Yan-E Du, Gang Tu, Guanglun Yang, Genyou Li, Dan Yang, Lei Lang, Lei Xi, Kexin Sun, Yanlin Chen, Kunxian Shu, Huadong Liao, Manran Liu, Yixuan Hou
Tumor microenvironment contributes to tumor angiogenesis. However, the role of the activated cancer associated-fibroblasts (CAFs) in angiogenesis is still unclear. Here we report that miR-205/YAP1 signaling in the activated stromal fibroblasts plays a critical role in VEGF-independent angiogenesis in breast tumor. Methods: miR-205 expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR); YAP1 expression by qRT-PCR, western blotting and immunohistochemistry; IL11 and IL15 expression by qRT-PCR, western blotting and ELISA...
2017: Theranostics
https://www.readbyqxmd.com/read/29108245/reversion-of-epithelial-mesenchymal-transition-by-a-novel-agent-dz-50-via-igf-binding-protein-3-in-prostate-cancer-cells
#19
Zheng Cao, Shahriar Koochekpour, Stephen E Strup, Natasha Kyprianou
Dysregulation of transforming growth factor-β1 (TGF-β1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107591/naked-mole-rat-induced-pluripotent-stem-cells-and-their-contribution-to-interspecific-chimera
#20
Sang-Goo Lee, Aleksei E Mikhalchenko, Sun Hee Yim, Alexei V Lobanov, Jin-Kyu Park, Kwang-Hwan Choi, Roderick T Bronson, Chang-Kyu Lee, Thomas J Park, Vadim N Gladyshev
Naked mole rats (NMRs) are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs) from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns...
November 14, 2017: Stem Cell Reports
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