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https://www.readbyqxmd.com/read/28534507/cecr1-mediated-cross-talk-between-macrophages-and-vascular-mural-cells-promotes-neovascularization-in-malignant-glioma
#1
C Zhu, I Chrifi, D Mustafa, M van der Weiden, P J M Leenen, D J Duncker, J M Kros, C Cheng
Glioblastomas (glioblastoma multiforme, GBM) are most malignant brain tumors characterized by profound vascularization. The activation of macrophages strongly contributes to tumor angiogenesis during GBM development. Previously, we showed that extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) is highly expressed by M2-like macrophages in GBM where it defines macrophage M2 polarization and contributes to tumor expansion. In this study, the effect of CECR1 in macrophages on tumor angiogenesis was investigated...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28531107/analysis-of-gene-expression-signatures-in-cancer-associated-stroma-from-canine-mammary-tumours-reveals-molecular-homology-to-human-breast-carcinomas
#2
Julia Ettlin, Elena Clementi, Parisa Amini, Alexandra Malbon, Enni Markkanen
Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526409/expression-and-purification-of-functional-pdgf-receptor-beta
#3
Qingbin Shang, Liang Zhao, Xiaojing Wang, Meimei Wang, Sen-Fang Sui, Li-Zhi Mi
Platelet Derived Growth Factor receptors (PDGFRs), members of receptor tyrosine kinase superfamily, play essential roles in early hematopoiesis, angiogenesis and organ development. Dysregulation of PDGF receptor signaling under pathological conditions associates with cancers, vascular diseases, and fibrotic diseases. Therefore, they are attractive targets in drug development. Like any other membrane proteins with a single-pass transmembrane domain, the high-resolution structural information of the full-length PDGF receptors is still not resolved...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28524160/stroma-regulated-hmga2-is-an-independent-prognostic-marker-in-pdac-and-aac
#4
Carina Strell, Karin Jessica Norberg, Artur Mezheyeuski, Jonas Schnittert, Praneeth R Kuninty, Carlos Fernández Moro, Janna Paulsson, Nicolai Aagaard Schultz, Dan Calatayud, Johannes Matthias Löhr, Oliver Frings, Caroline Sophie Verbeke, Rainer Lothar Heuchel, Jai Prakash, Julia Sidenius Johansen, Arne Östman
BACKGROUND: The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS: We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. RESULTS: HMGA2 acts as an independent prognostic marker associated with a significantly shorter overall survival in both tumour types...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#5
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28506734/mtor-vegf-pdgfr-and-c-kit-signaling-pathway-activation-in-kaposi-sarcoma
#6
Darcy A Kerr, Satya Vara Prasad Busarla, Devon C Gimbel, Aliyah R Sohani, Rosalynn M Nazarian
Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (n=274), most (90%) associated with human immunodeficiency virus (HIV)...
May 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28474091/cardiac-intimal-sarcoma-with-pdgfr%C3%AE-mutation-and-co-amplification-of-pdgfr%C3%AE-and-mdm2-an-autopsy-case-analyzed-by-whole-exome-sequencing
#7
Yukinobu Ito, Daichi Maeda, Makoto Yoshida, Akihiko Yoshida, Yukitsugu Kudo-Asabe, Hiroshi Nanjyo, Chikako Izumi, Fumio Yamamoto, Masahiro Inoue, Hiroyuki Shibata, Hiroto Katoh, Shumpei Ishikawa, Hiromi Nakamura, Yasushi Totoki, Tatsuhiro Shibata, Shinichi Yachida, Akiteru Goto
No abstract text is available yet for this article.
May 4, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28457731/expression-pattern-of-cancer-associated-fibroblast-and-its-clinical-relevance-in-intrahepatic-cholangiocarcinoma
#8
Xiao-Fang Zhang, Min Dong, Yu-Hang Pan, Jian-Ning Chen, Xiang-Qi Huang, Yi Jin, Chun-Kui Shao
Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and lacks of effective treatment, characterized by dense desmoplastic stroma rich in cancer-associated fibroblasts (CAFs), which have been indicated to facilitate tumor progression in several types of human cancer. However, the clinical relevance of CAFs in ICC has not been fully characterized. Here, we evaluated the histological phenotype of CAFs and immunohistochemical expressions of α-SMA, FSP-1, and PDGFRβ in 71 ICC cases, and found that immature CAF phenotype was significantly associated with lymph node metastasis (P=...
April 27, 2017: Human Pathology
https://www.readbyqxmd.com/read/28441414/regional-early-and-progressive-loss-of-brain-pericytes-but-not-vascular-smooth-muscle-cells-in-adult-mice-with-disrupted-platelet-derived-growth-factor-receptor-%C3%AE-signaling
#9
Angeliki Maria Nikolakopoulou, Zhen Zhao, Axel Montagne, Berislav V Zlokovic
Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain...
2017: PloS One
https://www.readbyqxmd.com/read/28436498/integrative-meta-modeling-identifies-endocytic-vesicles-late-endosome-and-the-nucleus-as-the-cellular-compartments-primarily-directing-rtk-signaling
#10
Jared C Weddell, Princess I Imoukhuede
Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling...
May 22, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28433542/blockade-of-pdgf-receptors-by-crenolanib-has-therapeutic-effect-in-patient-fibroblasts-and-in-preclinical-models-of-systemic-sclerosis
#11
Katsunari Makino, Tomoko Makino, Lukasz Stawski, Julio C Mantero, Robert Lafyatis, Robert Simms, Maria Trojanowska
Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. PDGF, a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II (Ang II)-induced skin and heart fibrosis...
April 19, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28424212/pdgf-receptor-%C3%AE-uses-akt-mtorc1-signaling-node-to-promote-high-glucose-induced-renal-proximal-tubular-cell-collagen-i-%C3%AE-2-expression
#12
Falguni Das, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in the diabetic renal proximal tubules. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting in the phosphorylation of the phosphatidylinositol 3 kinase...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28362700/dermatofibrosarcoma-protuberans-an-immunomarker-study-of-57-cases-that-included-putative-mesenchymal-stem-cell-markers
#13
Joon Seon Song, Eun-Ju Kim, Chan-Sik Park, Kyung-Ja Cho
Dermatofibrosarcoma protuberans (DFSP) is a low-grade fibroblastic sarcoma with a superficial location that has been suggested to potentially be a type of mesenchymal stem cell tumor. We studied the expression of various immunomarkers, including putative stem cell markers, in a series of 57 DFSPs including variants, and 12 dermatofibromas (DFs). CD105, a mesenchymal stem cell marker, was weakly expressed in 24 DFSPs, whereas other stem cell markers, including CD133, ALK-1, and Oct3/4, were completely negative in all samples...
March 30, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28345526/aspects-of-pericytes-and-their-potential-therapeutic-use
#14
Justyna Różycka, Edyta Brzóska, Tomasz Skirecki
Pericytes, which are multi-potential stem cells, co-create the walls of the microvessels: capillaries, terminal arterioles and postcapillary venules. These cells are localized under the basement membrane, tightly encircling the endothelium. The most frequently mentioned molecular markers of pericytes include NG2 (neural-glial antigen 2), β-type platelet-derived growth factor receptor (PDGFRβ), smooth muscle α-actin (α-SMA), regulator of G protein signalling 5 (RGS5), the adhesion protein CD146 and nestin...
March 13, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28339027/su6668-modulates-prostate-cancer-progression-by-downregulating-mtdh-akt-signaling-pathway
#15
Benjiang Qian, Yi Yao, Changming Liu, Jiabing Zhang, Huihong Chen, Huizhang Li
Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28333941/phenotypically-heterogeneous-podoplanin-expressing-cell-populations-are-associated-with-the-lymphatic-vessel-growth-and-fibrogenic-responses-in-the-acutely-and-chronically-infarcted-myocardium
#16
Maria Cimini, Antonio Cannatá, Gianandrea Pasquinelli, Marcello Rota, Polina Goichberg
Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts...
2017: PloS One
https://www.readbyqxmd.com/read/28289267/dual-role-of-pericyte-%C3%AE-6%C3%AE-1-integrin-in-tumour-blood-vessels
#17
Louise E Reynolds, Gabriela D'Amico, Tanguy Lechertier, Alexandros Papachristodoulou, José M Muñoz-Félix, Adèle De Arcangelis, Marianne Baker, Bryan Serrels, Kairbaan M Hodivala-Dilke
The integrin α6β1 is a major laminin receptor, and formation of a laminin-rich basement membrane is a key feature in tumour blood vessel stabilisation and pericyte recruitment; processes that are important in the growth and maturation of tumour blood vessels. However, the role of pericyte α6β1-integrin in angiogenesis is largely unknown. We developed mice where the α6-integrin subunit is deleted in pericytes and examined tumour angiogenesis and growth. These mice had: i) reduced pericyte coverage of tumour blood vessels; ii) reduced tumour blood vessel stability; iii) increased blood vessel diameter; iv) enhanced leakiness and, v) abnormal blood vessel basement membrane architecture...
March 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28268217/a-phenanthrene-derivative-5-7-dimethoxy-1-4-phenanthrenequinone-inhibits-cell-adhesion-molecule-expression-and-migration-in-vascular-endothelial-and-smooth-muscle-cells
#18
Huey-Ming Lo, Tsong-Long Hwang, Wen-Bin Wu
The activation of endothelial cells (ECs) and migration of vascular smooth muscle cells (VSMCs) have played a crucial role in monocyte chemotaxis/adhesion and intima thickening during vascular injury and atherosclerosis, respectively. Several phenanthrenes isolated from plants and natural products have been shown to possess different bioactivities such as anti-platelet aggregation and anti-inflammation. The current study was designated to investigate the effects of a phenanthrene derivative, 5,7-dimethoxy-1,4-phenanthrenequinone (DMPQ), on cell adhesion molecule (CAM) expression in vascular ECs and migration in VSMCs...
2017: Pharmacology
https://www.readbyqxmd.com/read/28259995/microrna-182-prevents-vascular-smooth-muscle-cell-dedifferentiation-via-fgf9-pdgfr%C3%AE-signaling
#19
Nana Dong, Wei Wang, Jinwei Tian, Zulong Xie, Bo Lv, Jiannan Dai, Rui Jiang, Dan Huang, Shaohong Fang, Jiangtian Tian, Hulun Li, Bo Yu
The abnormal phenotypic transformation of vascular smooth muscle cells (SMCs) causes various proliferative vascular diseases. MicroRNAs (miRNAs or miRs) have been established to play important roles in SMC biology and phenotypic modulation. This study revealed that the expression of miR‑182 was markedly altered during rat vascular SMC phenotypic transformation in vitro. We aimed to investigate the role of miR‑182 in the vascular SMC phenotypic switch and to determine the potential molecular mechanisms involved...
April 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28254885/neuropilin-1-binds-pdgf-d-and-is-a-co-receptor-in-pdgf-d-pdgfr%C3%AE-signaling
#20
Lars Muhl, Erika Bergsten Folestad, Hanna Gladh, Yixin Wang, Christine Moessinger, Lars Jakobsson, Ulf Eriksson
Platelet-derived growth factor (PDGF)-D is a PDGF receptor β (PDGFRβ)-specific ligand implicated in a number of pathological conditions, such as cardiovascular disease and cancer, but its biological function remains incompletely understood. In this study, we demonstrate that PDGF-D binds directly to neuropilin 1 (NRP1), in a manner that requires the PDGF-D C-terminal Arg residue. Stimulation with PDGF-D, but not PDGF-B, induced PDGFRβ-NRP1 complex formation in fibroblasts. Additionally, PDGF-D induced translocation of NRP1 to cell-cell junctions in endothelial cells, independently of PDGFRβ, altering the availability of NRP1 for VEGF-A-VEGFR2 signaling...
April 15, 2017: Journal of Cell Science
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