A novel fragment derived from the β chain of human fibrinogen, β43–63, is a potent inhibitor of activated endothelial cells in vitro and in vivo

Krajewska, E.; Ce, Lewis; Yy, Chen; Welford, Abigail; Tazzyman, Simon; Ca, Staton

doi:10.1038/sj.bjc.6605495

Cited by 16 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The fragment released after plasmin cleavage of fibrin had no effect on EC proliferation or migration, but inhibited tubule formation partly owing to cytotoxic effects on ECs. Moreover, Bβ43-63 reduced adhesion of ECs to the extracellular matrix by binding to and blocking integrin α V β 3 , exhibiting antiangiogenic and antitumor properties (73).…”

Section: Fibrin Fragmentsmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

206

139

View full text Add to dashboard Cite

Coagulation is fundamental for the confinement of infection and/or the inflammatory response to a limited area. Under pathological inflammatory conditions such as arthritis, multiple sclerosis or sepsis, an uncontrolled activation of the coagulation system contributes to inflammation, microvascular failure and organ dysfunction. Coagulation is initiated by the activation of thrombin, which, in turn, triggers fibrin formation by the release of fibrinopeptides. Fibrin is cleaved by plasmin, resulting in clot lysis and an accompanied generation of fibrin fragments such as D and E fragments. Various coagulation factors, including fibrinogen and/or fibrin [fibrin(ogen)] and also fibrin degradation products, modulate the inflammatory response by affecting leukocyte migration and cytokine production. Fibrin fragments are mostly proinflammatory, however, Bβ15-42 in particular possesses potential antiinflammatory effects. Bβ15-42 inhibits Rho-kinase activation by dissociating Fyn from Rho and, hence prevents stress-induced loss of endothelial barrier function and also leukocyte migration. This article summarizes the state-of-the-art in inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role fibrin fragments play during inflammation and, possibly, disease development.

show abstract

Section: Fibrin Fragmentsmentioning

confidence: 99%

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Jennewein

Tran

Paulus

et al. 2011

Mol Med

206

139

View full text Add to dashboard Cite

show abstract

“…Other anti-cancer serum components are also involved in inhibiting angiogenesis, such as the fibrinogen β chain, anastellin, and the cardioprotective protein, apolipoprotein A-1. In mouse models, the first 20 amino acids of the N terminus of the fibrinogen β chain (β43-63) haven been found to significantly inhibit tumor vascularization and increase tumor necrosis [71]. Anastellin, a fragment of the first type II module of fibronectin, has been found to inhibit tumor growth and metastasis in vivo through its inhibitory effects on angiogenesis [72,73].…”

Section: Human Serum Protein Components Recognized By Cigg And/or Ca215mentioning

confidence: 99%

“…Biomarker of ovarian cancer [89] Net functional effects include a decrease in tumor growth, angiogenesis, metastasis, invasion, & myeloid-derived suppressor cell recruitment, as well as an increase in antitumor macrophages & CD8 + T cells cells [74] Apolipoprotein A-1-deficient mice develop tumors quicker than wild-type mice [74] Fibrinogen β chain First 20 amino acids of the N terminus of the fibrinogen beta chain (β43-63) significantly inhibits VEGF-activated adhesion of epithelial cells to the extracellular matrix [71] In mouse models, inhibits tumor vascularization & increases tumor necrosis [71] Others:…”

Section: Anastellinmentioning

confidence: 99%

Cancerous Immunoglobulins in Cancer Immunology

2014

J Clin Cell Immunol

View full text Add to dashboard Cite

The expression of immunoglobulins by cancer cells have been known for two decades. However, the mechanisms of action behind these cancerous immunoglobulins (cIgG) are not well understood and may be different from immunoglobulins secreted by normal B lymphocytes. Therefore, the structural and functional roles of cIgG have been actively investigated to resolve this mystery. A monoclonal antibody, RP215, was generated in 1987 and was shown to react with a carbohydrate-associated epitope localized mainly on the heavy chains of cIgG but not on normal immunoglobulins. The knowledge of cIgG has been greatly advanced by using RP215 as a unique probe. Not only was RP215 shown to act as an anti-cIgG to induce apoptosis of cultured cancer cells in vitro/in vivo, it was also shown to elicit complement-dependent cytotoxicity (CDC) reactions to trigger lysis of cancer cells. It has now been established that besides serving to preserve growth/proliferation of cancer cells by capturing growth factors from the human serum, cIgG may also interact with certain human serum proteins which may be harmful to cancer cells. Thus, the hypothesis of dual functional roles of cIgG can be adequately explained in cancer immunology. Furthermore, RP215 may also be used to target cancer cells with surface bound cIgG for development of antibodybased anti-cancer drugs, provided that bioequivalent humanized RP215 is available for preclinical and clinical studies of immunotherapy.

show abstract

“…The first 20 amino acid of N terminus of the fibrinogen beta chain (β43-63) significantly inhibit VEGF-activation of epithelial cells to the extracellular matrix, and tumor vascularization and increase tumor necrosis [45]. Therefore, Fibrinonectin β chain which interacts with cIgG or CA215 is considered to exhibit anti-cancer properties in human body [45,46]. 4.…”

Section: Human Serum Proteins Exhibiting Anti-cancer Properties and Imentioning

confidence: 99%

“…Fibrinonectin β chain is one of the peptide chains required for the assembly of fibrinogen involved in the formation of blood clot [45,46]. The first 20 amino acid of N terminus of the fibrinogen beta chain (β43-63) significantly inhibit VEGF-activation of epithelial cells to the extracellular matrix, and tumor vascularization and increase tumor necrosis [45].…”

Section: Human Serum Proteins Exhibiting Anti-cancer Properties and Imentioning

confidence: 99%

Dual Differential Roles of Cancerous Immunoglobulins as Suggested by Interactions with Human Serum Proteins

Lee¹

2015

J Clin Cell Immunol

View full text Add to dashboard Cite

In search of functional roles of immunoglobulins expressed by cancer cells, molecular interactions between cancerous immunoglobulins and human serum proteins or protein fragments were investigated by using RP215 monoclonal antibody as the unique probe. RP215 was initially generated against OC-3-VGH ovarian cancer cell extract and shown to react with carbohydrate-associated epitope located mainly on the variable regions of immunoglobulin heavy chains and others expressed by cancer cells which are designated in general as CA215. CA215 and cancerous immunoglobulins (cIgG) were affinity isolated from the shed medium of cultured cancer cells. Furthermore, by using purified CA215 and cIgG as the respective affinity ligands, the serum proteins or components were affinity isolated and subject to analysis by LCMS/MS methods. The results of such analysis suggest that as many as 80-86% of the isolated human serum proteins were identical in those purified by either affinity column. They are generally classified as pro-cancer and anti-cancer protein components. Among the known pro-cancer protein components recognized by cancerous immunoglobulins are C4 binding proteins α-chain, complement C3, complement factor H, serotransferrin and vitronectin, etc. On the other hand, inter-α-trypsin inhibitor heavy chain 4, anastellin, apolipoprotein A1, fibrinogen β-chain and keratin type 1 cytoskeletal 9 or autoimmune IgG were considered to be anti-cancer proteins from human serum. Based on these observations, dual functional roles of cancerous immunoglobulins are hypothesized. It has been demonstrated in this study that cancerous immunoglobulins are capable of serving as specific binding protein-like immunoglobulins to capture serum proteins to promote growth of cancer cells. At the same time, they can neutralize those with anti-cancer properties in human circulations.

show abstract

A novel fragment derived from the β chain of human fibrinogen, β43–63, is a potent inhibitor of activated endothelial cells in vitro and in vivo

Cited by 16 publications

References 34 publications

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Novel Aspects of Fibrin(ogen) Fragments during Inflammation

Cancerous Immunoglobulins in Cancer Immunology

Dual Differential Roles of Cancerous Immunoglobulins as Suggested by Interactions with Human Serum Proteins

Contact Info

Product

Resources

About