Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

doi:10.1038/srep23613

Cited by 34 publications

(25 citation statements)

References 44 publications

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“…Human specimens were purchased from BioChain Institute, Inc (Newark, CA, USA). Immunohistochemistry (IHC) was carried out as previously described . Anti‐TMEM180 antibody or anti‐EGFR mAb (cetuximab, Merck, Darmstadt, Germany) was labeled with HRP using Peroxidase Labeling Kit‐SH (Dojindo).…”

Section: Methodsmentioning

confidence: 99%

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Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer‐specific molecule

et al. 2019

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The present state of therapy for colorectal cancer (CRC) is far from satisfactory, highlighting the need for new targets for this disease. We identified a new CRC‐specific molecule, TMEM180, a predicted 11‐pass transmembrane protein that apparently functions as a cation symporter. We developed an anti‐TMEM180 mAb and then succeeded in humanizing the mAb. Immunohistochemistry (IHC) in CRC with the mAb showed a similar positivity rate as compared with anti‐epidermal growth factor receptor mAb, and IHC with anti‐TMEM180 mAb did not show staining in major organs used in this study. Immune electron microscopy clearly indicated that TMEM180 was present on the tumor exosome. The TMEM180 promoter region contains 10 hypoxia‐responsive element consensus sequences; accordingly, SW480 cells upregulated TMEM180 under low‐oxygen conditions. Anti‐TMEM180 mAb has in vitro antibody‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity activity, and SW480 CRC xenografts were eradicated by the mAb. These data indicate that TMEM180 may be a new CRC marker and that a mAb against this protein could be used as antibody‐based therapy against CRC.

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Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry (IHC) was carried out as previously described. 15 Anti-TMEM180 antibody or anti-EGFR mAb (cetuximab, Merck, Darmstadt, Germany) was labeled with HRP using Peroxidase Labeling Kit-SH (Dojindo). Tissues were then incubated with the HRP-conjugated anti-TMEM180 mAb or anti-EGFR mAb for 1 hour at room temperature.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer‐specific molecule

et al. 2019

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“…Cross‐linked fibrin and FBG‐related proteins are deposited extravascularly from the local hypermeable blood vessels within tumor stroma, and they play important roles in the pathogenesis of tumor growth and spread . The tumor stroma and the local ECM is a versatile environment where coagulation‐related events (i.e., platelet activation, fibrin clot deposition, fibrinolysis) are activated by cancer, and their biochemical composition is dramatically affected by tumor cell growth and its further metastasis, accompanied by tumor‐driven production and release of specific factors (e.g., proinflammatory, prothrombotic, and proangiogenic) …”

Section: Introduction: the Coagulation Processmentioning

confidence: 99%

Coagulation and fibrinolysis in gastric cancer

Repetto

2017

Annals of the New York Academy of Sciences

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Coagulation is a highly conserved process occurring after an injury to a blood vessel and resulting in hemostasis. In the thrombus microenvironment, finely orchestrated events restore vessel integrity through platelet activation, adhesion, and aggregation (primary hemostasis), followed by the coagulation cascades, thrombin generation, and fibrin clot deposition (secondary hemostasis). Several studies on cancer have provided insight into dramatic changes to coagulation-related events (i.e., fibrin clot deposition, fibrinolysis) during tumor pathogenesis, progression, and metastasis, in addition to a tumor-driven systemic activation of hemostasis and thrombosis (Trousseau's syndrome). Diverse molecular and cellular effectors participate in the cross talk between hemostasis and tumors. Here, we focus on some aspects of the interconnection between cancer biology and hemostatic components, with particular attention to some key coagulation-related proteins (e.g., tissue factor, thrombin, fibrinogen, and D-dimers) in the particular case of gastric cancer (GC). Recent advances in deciphering the complex molecular link between GC and the coagulation system are described, showing their important roles in better management of patients affected by GC.

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“…The expression of hS9-Fab03 in E. coli BL21 was detected by Western blotting as previously described (26). The concentrations of proteins were determined by bicinchoninic acid protein assay kit (Thermo, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

The Fab Fragment of a Human Anti-Siglec-9 Monoclonal Antibody Suppresses LPS-Induced Inflammatory Responses in Human Macrophages

et al. 2016

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Sepsis is a major cause of death for hospitalized patients and is characterized by massive overreaction of immune responses to invading pathogens which is mediated by cytokines. For decades, there has been no effective treatment for sepsis. Sialic acid-binding, Ig-like lectin-9 (Siglec-9), is an immunomodulatory receptor expressed primarily on hematopoietic cells which is involved in various aspects of inflammatory responses and is a potential target for treatment of sepsis. The aim of the present study was to develop a human anti-Siglec-9 Fab fragment, which was named hS9-Fab03 and investigate its immune activity in human macrophages. We began by constructing the hS9-Fab03 prokaryotic expression vector from human antibody library and phage display. Then, we utilized a multitude of assays, including SDS-PAGE, Western blotting, ELISA, affinity, and kinetics assay to evaluate the binding affinity and specificity of hS9-Fab03. Results demonstrated that hS9-Fab03 specifically bind to Siglec-9 antigen with high affinity, and pretreatment with hS9-Fab03 could attenuate lipopolysaccharide (LPS)-induced TNF-α, IL-6, IL-1β, IL-8, and IFN-β production in human PBMC-derived macrophages, but slightly increased IL-10 production in an early time point. We also observed similar results in human THP-1-differentiated macrophages. Collectively, we prepared the hS9-Fab03 with efficient activity for blocking LPS-induced pro-inflammatory cytokines production in human macrophages. These results indicated that ligation of Siglec-9 with hS9-Fab03 might be a novel anti-inflammatory therapeutic strategy for sepsis.

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Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Cited by 34 publications

References 44 publications

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer‐specific molecule

Significant antitumor effect of an antibody against TMEM180, a new colorectal cancer‐specific molecule

Coagulation and fibrinolysis in gastric cancer

The Fab Fragment of a Human Anti-Siglec-9 Monoclonal Antibody Suppresses LPS-Induced Inflammatory Responses in Human Macrophages

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