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Marcy C Purnell
Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred...
April 2017: Discovery Medicine
Jaime L Stafford, Gregory Dyson, Nancy K Levin, Sophia Chaudhry, Rita Rosati, Hasini Kalpage, Courtney Wernette, Nancie Petrucelli, Michael S Simon, Michael A Tainsky
While up to 25% of ovarian cancer (OVCA) cases are thought to be due to inherited factors, the majority of genetic risk remains unexplained. To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2. In silico SNP analysis was employed to identify suspect variants followed by validation using Sanger DNA sequencing...
2017: PloS One
Zhengcheng He, Nagarajan Kannan, Oksana Nemirovsky, Helen Chen, Marisa Connell, Brian Taylor, Jihong Jiang, Linda M Pilarski, Markus C Fleisch, Dieter Niederacher, Miguel Angel Pujana, Connie J Eaves, Christopher A Maxwell
BRCA1 deficiency may perturb the differentiation hierarchy present in the normal mammary gland and is associated with the genesis of breast cancers that are genomically unstable and typically display a basal-like transcriptome. Oriented cell division is a mechanism known to regulate cell fates and to restrict tumor formation. We now show that the cell division axis is altered following shRNA-mediated BRCA1 depletion in immortalized but non-tumorigenic, or freshly isolated normal human mammary cells with graded consequences in progeny cells that include aneuploidy, perturbation of cell polarity in spheroid cultures, and a selective loss of cells with luminal features...
May 16, 2017: Oncotarget
S B Bahrami, C Tolg, T Peart, C Symonette, M Veiseh, J U Umoh, D W Holdsworth, J B McCarthy, L G Luyt, M J Bissell, A Yazdani, E A Turley
Hyaluronan, CD44 and the Receptor for Hyaluronan-Mediated Motility (RHAMM, gene name HMMR) regulate stem cell differentiation including mesenchymal progenitor differentiation. Here, we show that CD44 expression is required for subcutaneous adipogenesis, whereas RHAMM expression suppresses this process. We designed RHAMM function blocking peptides to promote subcutaneous adipogenesis as a clinical and tissue engineering tool. Adipogenic RHAMM peptides were identified by screening for their ability to promote adipogenesis in culture assays using rat bone marrow mesenchymal stem cells, mouse pre-adipocyte cell lines and primary human subcutaneous pre-adipocytes...
March 1, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
Laura E Stevens, William K C Cheung, Sally J Adua, Anna Arnal-Estapé, Minghui Zhao, Zongzhi Liu, Kelly Brewer, Roy S Herbst, Don X Nguyen
Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression of a network of extracellular matrix (ECM) molecules and their interacting proteins contributes to risk of relapse in distinct LUAD subtypes. Overexpression of the hyaluronan receptor HMMR in primary LUAD was associated with an inflammatory molecular signature and poor prognosis. Attenuating HMMR in LUAD cells diminished their ability to initiate lung tumors and distant metastases...
April 15, 2017: Cancer Research
Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4-/CD8-/CD19- cell subpopulations were separated...
February 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Wei Liu, Jun Ma, Yong Cheng, Hongbo Zhang, Wengguang Luo, Hongyan Zhang
Recently, accumulating evidence has suggested that long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis and cancer progression. Hyaluronan-mediated motility receptor (HMMR) is an essential cancer-related gene in basal-like breast cancer (BLBC). In our study, HMMR antisense RNA 1 (HMMR-AS1) was analyzed in BLBC patients through polymerase chain reaction analysis. Here, we found that the expression of HMMR was positively correlated with HMMR-AS1 (RP11-80G.1). When HMMR-AS1 (RP11-80G.1) was knocked down, the expression of HMMR markedly reduced...
2016: Breast Cancer: Targets and Therapy
Yannick Willemen, Johan M J Van den Bergh, Sarah M Bonte, Sébastien Anguille, Carlo Heirman, Barbara M H Stein, Herman Goossens, Tessa Kerre, Kris Thielemans, Marc Peeters, Viggo F I Van Tendeloo, Evelien L J Smits, Zwi N Berneman
We formerly demonstrated that vaccination with Wilms' tumor 1 (WT1)-loaded autologous monocyte-derived dendritic cells (mo-DCs) can be a well-tolerated effective treatment in acute myeloid leukemia (AML) patients. Here, we investigated whether we could introduce the receptor for hyaluronic acid-mediated motility (RHAMM/HMMR/CD168), another clinically relevant tumor-associated antigen, into these mo-DCs through mRNA electroporation and elicit RHAMM-specific immune responses. While RHAMM mRNA electroporation significantly increased RHAMM protein expression by mo-DCs, our data indicate that classical mo-DCs already express and present RHAMM at sufficient levels to activate RHAMM-specific T cells, regardless of electroporation...
November 8, 2016: Oncotarget
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
N P Akent'eva, S S Shushanov, A I Kotel'nikov
RHAMM-selective peptides in a concentration of 10 μg/ml (2×10(-7) M) inhibited the growth of MDA-MB-231 breast cancer cells over 48 h. Treatment of cancer cells with RHAMM-selective peptides induced apoptosis and necrosis and increased caspase-3 activity (by 30%).
September 2015: Bulletin of Experimental Biology and Medicine
Kenneth Virgel N Esguerra, Cornelia Tolg, Natalia Akentieva, Matthew Price, Choi-Fong Cho, John D Lewis, James B McCarthy, Eva A Turley, Leonard G Luyt
Fragments of the extracellular matrix component hyaluronan (HA) promote tissue inflammation, fibrosis and tumor progression. HA fragments act through HA receptors including CD44, LYVE1, TLR2, 4 and the receptor for hyaluronan mediated motility (RHAMM/HMMR). RHAMM is a multifunctional protein with both intracellular and extracellular roles in cell motility and proliferation. Extracellular RHAMM binds directly to HA fragments while intracellular RHAMM binds directly to ERK1 and tubulin. Both HA and regions of tubulin (s-tubulin) are anionic and bind to basic amino acid-rich regions in partner proteins, such as in HA and tubulin binding regions of RHAMM...
December 2015: Integrative Biology: Quantitative Biosciences From Nano to Macro
W Zhou, M Yin, H Cui, N Wang, L-L Zhao, L-Z Yuan, X-P Yang, X-M Ding, F-Z Men, X Ma, J-R Na
OBJECTIVE: The study was aimed to explore the underlying mechanisms and identify the potential target genes by bioinformatics analysis for non-small-cell lung carcinoma (NSCLC) treatment in non-smoking women. MATERIALS AND METHODS: The microarray data of GSE19804 was downloaded from Gene Expression Omnibus (GEO) database. Paired samples (from the same patient) of tumor and normal lung tissues from 60 non-smoking female NSCLC patients were used to identify differentially expressed genes (DEGs)...
September 2015: European Review for Medical and Pharmacological Sciences
Biljana Stangeland, Awais A Mughal, Zanina Grieg, Cecilie Jonsgar Sandberg, Mrinal Joel, Ståle Nygård, Torstein Meling, Wayne Murrell, Einar O Vik Mo, Iver A Langmoen
Glioblastoma (GBM) is both the most common and the most lethal primary brain tumor. It is thought that GBM stem cells (GSCs) are critically important in resistance to therapy. Therefore, there is a strong rationale to target these cells in order to develop new molecular therapies.To identify molecular targets in GSCs, we compared gene expression in GSCs to that in neural stem cells (NSCs) from the adult human brain, using microarrays. Bioinformatic filtering identified 20 genes (PBK/TOPK, CENPA, KIF15, DEPDC1, CDC6, DLG7/DLGAP5/HURP, KIF18A, EZH2, HMMR/RHAMM/CD168, NOL4, MPP6, MDM1, RAPGEF4, RHBDD1, FNDC3B, FILIP1L, MCC, ATXN7L4/ATXN7L1, P2RY5/LPAR6 and FAM118A) that were consistently expressed in GSC cultures and consistently not expressed in NSC cultures...
September 22, 2015: Oncotarget
Maria A Missinato, Kimimasa Tobita, Nicla Romano, James A Carroll, Michael Tsang
AIMS: After injury, the adult zebrafish can regenerate the heart. This requires the activation of the endocardium and epicardium as well as the proliferation of pre-existing cardiomyocytes to replace the lost tissue. However, the molecular mechanisms involved in this process are not completely resolved. In this work, we aim to identify the proteins involved in zebrafish heart regeneration and to explore their function. METHODS AND RESULTS: Using a proteomic approach, we identified Hyaluronan-mediated motility receptor (Hmmr), a hyaluronic acid (HA) receptor, to be expressed following ventricular resection in zebrafish...
September 1, 2015: Cardiovascular Research
Kathryn L Schwertfeger, Mary K Cowman, Patrick G Telmer, Eva A Turley, James B McCarthy
Breast cancer-induced inflammation in the tumor reactive stroma supports invasion and malignant progression and is contributed to by a variety of host cells including macrophages and fibroblasts. Inflammation appears to be initiated by tumor cells and surrounding host fibroblasts that secrete pro-inflammatory cytokines and chemokines and remodel the extracellular matrix (ECM) to create a pro-inflammatory "cancerized" or tumor reactive microenvironment that supports tumor expansion and invasion. The tissue polysaccharide hyaluronan (HA) is an example of an ECM component within the cancerized microenvironment that promotes breast cancer progression...
2015: Frontiers in Immunology
Mary K Cowman, Hong-Gee Lee, Kathryn L Schwertfeger, James B McCarthy, Eva A Turley
Hyaluronan is a simple repeating disaccharide polymer, synthesized at the cell surface by integral membrane synthases. The repeating sequence is perfectly homogeneous, and is the same in all vertebrate tissues and fluids. The polymer molecular mass is more variable. Most commonly, hyaluronan is synthesized as a high-molecular mass polymer, with an average molecular mass of approximately 1000-8000 kDa. There are a number of studies showing increased hyaluronan content, but reduced average molecular mass with a broader range of sizes present, in tissues or fluids when inflammatory or tissue-remodeling processes occur...
2015: Frontiers in Immunology
Huilei Zhou, Lin Wang, Juxiang Huang, Minghu Jiang, Xiaoyu Zhang, Liyuan Zhang, Yangming Wang, Zhenfu Jiang, Zhongjie Zhang
48 different Pearson mutual-positive-correlation epidermal growth factor receptor (EGFR_1)-activatory molecular feedback, up- and down-stream network was constructed from 171 overlapping of 366 GRNInfer and 223 Pearson under EGFR_1 CC ≥0.25 in high lung adenocarcinoma compared with low human normal adjacent tissues. Our identified EGFR_1 inside-out upstream activated molecular network showed SLC2A1 (solute carrier family 2 (facilitated glucose transporter) member 1), CCNB2 (cyclin B2), HMMR (hyaluronan-mediated motility receptor (RHAMM)), KIF11 (kinesin family member 11), NUSAP1 (nucleolar and spindle associated protein 1), PRC1 (protein regulator of cytokinesis 1), UBE2C (ubiquitin-conjugating enzyme E2C) in high lung adenocarcinoma...
2015: Journal of Cancer
Ignacio Blanco, Karoline Kuchenbaecker, Daniel Cuadras, Xianshu Wang, Daniel Barrowdale, Gorka Ruiz de Garibay, Pablo Librado, Alejandro Sánchez-Gracia, Julio Rozas, Núria Bonifaci, Lesley McGuffog, Vernon S Pankratz, Abul Islam, Francesca Mateo, Antoni Berenguer, Anna Petit, Isabel Català, Joan Brunet, Lidia Feliubadaló, Eva Tornero, Javier Benítez, Ana Osorio, Teresa Ramón y Cajal, Heli Nevanlinna, Kristiina Aittomäki, Banu K Arun, Amanda E Toland, Beth Y Karlan, Christine Walsh, Jenny Lester, Mark H Greene, Phuong L Mai, Robert L Nussbaum, Irene L Andrulis, Susan M Domchek, Katherine L Nathanson, Timothy R Rebbeck, Rosa B Barkardottir, Anna Jakubowska, Jan Lubinski, Katarzyna Durda, Katarzyna Jaworska-Bieniek, Kathleen Claes, Tom Van Maerken, Orland Díez, Thomas V Hansen, Lars Jønson, Anne-Marie Gerdes, Bent Ejlertsen, Miguel de la Hoya, Trinidad Caldés, Alison M Dunning, Clare Oliver, Elena Fineberg, Margaret Cook, Susan Peock, Emma McCann, Alex Murray, Chris Jacobs, Gabriella Pichert, Fiona Lalloo, Carol Chu, Huw Dorkins, Joan Paterson, Kai-Ren Ong, Manuel R Teixeira, Frans B L Hogervorst, Annemarie H van der Hout, Caroline Seynaeve, Rob B van der Luijt, Marjolijn J L Ligtenberg, Peter Devilee, Juul T Wijnen, Matti A Rookus, Hanne E J Meijers-Heijboer, Marinus J Blok, Ans M W van den Ouweland, Cora M Aalfs, Gustavo C Rodriguez, Kelly-Anne A Phillips, Marion Piedmonte, Stacy R Nerenstone, Victoria L Bae-Jump, David M O'Malley, Elena S Ratner, Rita K Schmutzler, Barbara Wappenschmidt, Kerstin Rhiem, Christoph Engel, Alfons Meindl, Nina Ditsch, Norbert Arnold, Hansjoerg J Plendl, Dieter Niederacher, Christian Sutter, Shan Wang-Gohrke, Doris Steinemann, Sabine Preisler-Adams, Karin Kast, Raymonda Varon-Mateeva, Andrea Gehrig, Anders Bojesen, Inge Sokilde Pedersen, Lone Sunde, Uffe Birk Jensen, Mads Thomassen, Torben A Kruse, Lenka Foretova, Paolo Peterlongo, Loris Bernard, Bernard Peissel, Giulietta Scuvera, Siranoush Manoukian, Paolo Radice, Laura Ottini, Marco Montagna, Simona Agata, Christine Maugard, Jacques Simard, Penny Soucy, Andreas Berger, Anneliese Fink-Retter, Christian F Singer, Christine Rappaport, Daphne Geschwantler-Kaulich, Muy-Kheng Tea, Georg Pfeiler, Esther M John, Alex Miron, Susan L Neuhausen, Mary Beth Terry, Wendy K Chung, Mary B Daly, David E Goldgar, Ramunas Janavicius, Cecilia M Dorfling, Elisabeth J van Rensburg, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Andrew K Godwin, Edith Olah, Steven A Narod, Gad Rennert, Shani Shimon Paluch, Yael Laitman, Eitan Friedman, Annelie Liljegren, Johanna Rantala, Marie Stenmark-Askmalm, Niklas Loman, Evgeny N Imyanitov, Ute Hamann, Amanda B Spurdle, Sue Healey, Jeffrey N Weitzel, Josef Herzog, David Margileth, Chiara Gorrini, Manel Esteller, Antonio Gómez, Sergi Sayols, Enrique Vidal, Holger Heyn, Dominique Stoppa-Lyonnet, Melanie Léoné, Laure Barjhoux, Marion Fassy-Colcombet, Antoine de Pauw, Christine Lasset, Sandra Fert Ferrer, Laurent Castera, Pascaline Berthet, François Cornelis, Yves-Jean Bignon, Francesca Damiola, Sylvie Mazoyer, Olga M Sinilnikova, Christopher A Maxwell, Joseph Vijai, Mark Robson, Noah Kauff, Marina J Corines, Danylko Villano, Julie Cunningham, Adam Lee, Noralane Lindor, Conxi Lázaro, Douglas F Easton, Kenneth Offit, Georgia Chenevix-Trench, Fergus J Couch, Antonis C Antoniou, Miguel Angel Pujana
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach...
2015: PloS One
J L Huan, X Gao, L Xing, X J Qin, H X Qian, Q Zhou, L Zhu
The aim of this study was to identify key genes related to invasive ductal carcinoma (IDC) of the breast by analyzing gene expression data with bioinformatic tools. Microarray data set GSE31138 was downloaded from Gene Expression Omnibus, including 3 breast cancer tissue samples and 3 normal controls. Differentially expressed genes (DEGs) between breast cancer and normal control were screened out (FDR < 0.05 and |logFC| > 2). Coexpression between genes was examined with String, and a network was then constructed...
2014: Genetics and Molecular Research: GMR
Kimberley Joanne Hatfield, Håkon Reikvam, Øystein Bruserud
OBJECTIVE: The malignant cell population of acute myeloid leukemia (AML) includes a small population of stem/progenitor cells with long-term in vitro proliferation. We wanted to compare long-term AML cell proliferation for unselected patients, investigate the influence of endothelial cells on AML cell proliferation and identify biological characteristics associated with clonogenic capacity. METHODS: Cells were cultured in medium supplemented with recombinant growth factors FMS-like tyrosine kinase-3 ligand, stem cell factor, IL-3, G-CSF and thrombopoietin...
November 2014: Expert Opinion on Therapeutic Targets
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