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Your search keyword '"Francis P. Roche"' showing total 2 results
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1. Marginal zone lymphoma expression of histidine‐rich glycoprotein correlates with improved survival

Author

Tor Persson Skare, Elin Sjöberg, Mattias Berglund, Ross O Smith, Francis P Roche, Cecilia Lindskog, Birgitta Sander, Ingrid Glimelius, Alex R Gholiha, Gunilla Enblad, Rose‐Marie Amini, and Lena Claesson‐Welsh

Subjects
alpha defensin 1, gene expression, histidine rich glycoprotein, marginal zone lymphoma, survival, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Purpose The abundant hepatocyte‐expressed plasma protein histidine‐rich glycoprotein (HRG) enhances antitumor immunity by polarizing inflammatory and immune cells in several mouse models, however, the clinical relevance of HRG in human cancer is poorly explored. The expression and role of HRG in human B‐cell lymphomas was investigated in order to find new tools for prognosis and treatment. Findings Immunohistochemical (IHC) analysis and RNA hybridization of tissue microarrays showed that (i) HRG was expressed by tumor cells in marginal zone lymphoma (MZL), in 36% of 59 cases. Expression was also detected in follicular lymphoma (22%), mantle cell lymphoma (19%), and indiffuse large B‐cell lymphoma (DLBCL;5%) while primary CNS lymphoma (PCNSL) lacked expression of HRG. (ii) MZL patients positive for HRG showed a superior overall survival outcome (HR = 0.086, 95% CI = 0.014‐0.518, P‐value = .007), indicating a protective role for HRG independent of stage, age and sex. (iii) HRG‐expressing MZL displayed significantly increased transcript and protein levels of the host defense peptide alpha defensin 1. In addition, global transcript analyses showed significant changes in gene ontology terms relating to immunity and inflammation, however, infiltration of immune and inflammatory cells detected by IHC was unaffected by HRG expression. Conclusion HRG expression by MZL tumor cells correlates with an altered transcription profile and improved overall survival.

Published
2020
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2. Histidine-rich glycoprotein blocks collagen-binding integrins and adhesion of endothelial cells through low-affinity interaction with α2 integrin

Author

Satoshi Honjo, Kalle Sipilä, Jyrki Heino, Sonia Tugues, Staffan Johansson, Francis P. Roche, and Lena Claesson-Welsh

Subjects
Vascular Endothelial Growth Factor A, Histidine-rich glycoprotein, Integrin, Gene Expression, Plasma protein binding, Cell Line, Extracellular matrix, Myoblasts, chemistry.chemical_compound, Mice, Cell Adhesion, Human Umbilical Vein Endothelial Cells, Animals, Humans, Binding site, Cell adhesion, Molecular Biology, biology, Chemotaxis, ta1182, Proteins, Heparan sulfate, Molecular biology, Recombinant Proteins, Protein Structure, Tertiary, Mice, Inbred C57BL, Protein Subunits, chemistry, Ectodomain, biology.protein, Female, Heparitin Sulfate, Integrin alpha2beta1, Protein Binding
Abstract

The plasma protein histidine-rich glycoprotein (HRG) affects the morphology and function of both endothelial cells (ECs) and monocytes/macrophages in cancer. Here, we examined the mechanism of action of HRG's effect on ECs. HRG suppressed adhesion, spreading and migration of ECs specifically on collagen I (COL I) whereas ECs seeded on other extracellular matrix proteins were insensitive to HRG. HRG did not bind specifically to COL I or to the α-integrin binding site on collagen, GFOGER. Furthermore, HRG's inhibition of EC adhesion was not dependent upon heparan sulfate (HS) moieties as heparitinase-treated ECs remained sensitive to HRG. C2C12 cells expressing α2 integrin, the major collagen-binding α-integrin subunit in ECs, showed increased binding of HRG compared with wild type C2C12 cells lacking the α2 subunit. Recombinant α2 I-domain protein bound HRG and to a higher extent when in active conformation. However, the α2 I-domain bound weakly to HRG compared with COL I and the purified α2β1 ectodomain complex failed to retain HRG. We conclude that HRG binds to α2 integrin through low-affinity interactions in a HS-independent manner, thereby blocking EC-adhesion to COL I.

Published
2015

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