Factor H co-purifies with thrombospondin isolated from platelet secretate

Carron, J.A.; Bates, Richard C.; Smith, A. Ian; Tetoz, T.; Arellano, Alejandro; Gordon, David L.; Burns, Gordon F.

doi:10.1016/0304-4165(95)00095-x

Cited by 16 publications

(14 citation statements)

References 26 publications

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“…Other ligands of TSP1 with possible function in hemostasis TSP1 interacts with other molecules with known or putative regulatory functions in atherothrombosis, including adiponectin [77], histidine-rich glycoprotein [78], galectin [79], complement factor H [80], matrix metalloproteinase-2 [81], lysosomal integral membrane protein II (LIMPII), a protein member of the CD36 family [82], the heavy chain of elastaseactivated coagulation factor V [83] and calreticulinlow density lipoprotein receptor-related protein receptor complex [84].…”

Section: Glycolipid Sulfatementioning

confidence: 99%

Thrombospondins: from structure to therapeutics

Bonnefoy

Moura

Hoylaerts

2008

Cell. Mol. Life Sci.

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Thrombospondin-1 (TSP1) is a multi-domain, multi-functional glycoprotein synthesized by many cells. Matricellular TSP1 modulates cell adhesion and proliferation. TSP1 is involved in angiogenesis, inflammation, wound healing and cancer. As a major platelet protein, for a long time it was postulated to control hemostasis via platelet aggregate stabilization. However, these in vitro findings have been questioned in the absence of corroborating clinical data and of obvious hemostatic defects in TSP1 gene-deficient mice.Yet, the past few years have provided indices to implicate TSP1 in hemostasis. In clinical studies, a correlation exists between a welldefined TSP1 polymorphism and a significant risk of myocardial infarction. At the same time, recent in vivo animal model data imply TSP1 in the multimer size control of von Willebrand factor, in smooth muscle cell regulation and in vascular perfusion. These findings shed new light on the role of TSP1 in hemostasis and prothrombotic vascular pathologies. (Part of a Multi-author Review).

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Section: Glycolipid Sulfatementioning

confidence: 99%

Thrombospondins: from structure to therapeutics

Bonnefoy

Moura

Hoylaerts

2008

Cell. Mol. Life Sci.

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“…TSP-1 was purified from human platelets as described (21,22) by heparin affinity column with subsequent sizing chromatography on Sephacryl-200 (Pharmacia) and subjected to batch chromatography with gelatin Sepharose to eliminate possible fibronectin. Protein purity was assessed by 7.5% SDS͞PAGE, and no contaminating factor H was detected (23). Contamination with transforming growth factor-␤ that can copurify with thrombospondin was measured (24) and found to be Ͻ0.1 pg͞g protein.…”

Section: Methodsmentioning

confidence: 99%

A human fibrosarcoma inhibits systemic angiogenesis and the growth of experimental metastases via thrombospondin-1

Volpert

Lawler

Bouck

1998

Proc. Natl. Acad. Sci. U.S.A.

163

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Concomitant tumor resistance refers to the ability of some large primary tumors to hold smaller tumors in check, preventing their progressive growth. Here, we demonstrate this phenomenon with a human tumor growing in a nude mouse and show that it is caused by secretion by the tumor of the inhibitor of angiogenesis, thrombospondin-1. When growing subcutaneously, the human fibrosarcoma line HT1080 induced concomitant tumor resistance, preventing the growth of experimental B16͞F10 melanoma metastases in the lung. Resistance was due to the production by the tumor cells themselves of high levels of thrombospondin-1, which was present at inhibitory levels in the plasma of tumor-bearing animals who become unable to mount an angiogenic response in their corneas. Animals carrying tumors formed by antisense-derived subclones of HT1080 that secreted low or no thrombospondin had weak or no ability to control the growth of lung metastases. Although purified human platelet thrombospondin-1 had no effect on the growth of melanoma cells in vitro, when injected into mice it was able to halt the growth of their experimental metastases, providing clear evidence of the efficacy of thrombospondin-1 as an anti-tumor agent.Concomitant tumor resistance is an unusual phenomenon wherein animals harboring large primary tumors are resistant to the growth of distant smaller tumors (reviewed in refs. 1 and 2). This resistance depends on circulating factors and disappears upon surgical resection of the primary tumor. In stunning advances over the past several years, O'Reilly and Folkman (3-7) have shown that, in syngeneic rodent systems, the circulating factors responsible for such resistance are inhibitors of angiogenesis. Two of these have been identified: angiostatin and endostatin. In these model systems, primary tumors secrete inducers of angiogenesis and also generate inhibitors of angiogenesis. In the microenvironment of the large primary tumor, the inducers are apparently sufficient to overcome the effects of the inhibitors because the new vessels essential for progressive tumor growth are present. However, when inducers and inhibitors are shed from the tumor bed into the circulation, levels of the more labile inducers fall off rapidly whereas levels of the more stable inhibitors rise, creating a systemic antiangiogenic environment that prevents small nests of metastatic cells from inducing neovascularization. As a result, these incipient tumors remain small and dormant. On removal of the primary tumor, inhibitor levels fall and the previously dormant metastases expand vigorously.Concomitant tumor resistance likely also occurs in human cancer patients. There are a variety of anecdotal clinical reports in the literature describing the fast and disastrous development of what must have been preexisting metastases following surgical removal of a primary tumor, (for example, see ref. 8 and citations in refs. 1 and 2). One such case is that of the patient from whom the widely used human fibrosarcoma line HT1080 was derived and who d...

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Section: Discussionmentioning

confidence: 99%

“…Methods for the isolation of CFH from human, rat or mouse plasma on a laboratory scale have been published previously [20–26]. These methods have the disadvantage of combining immunadsorption [22,24], protein precipitation steps [21,25,26], affinity chromatography [23, 26], gel filtration [21,25] or addition of protease inhibitors [25,26] that are generally not recommended for large‐scale purification processes for technical and economic reasons. Because the importance of CFH as a potential therapeutic complement inhibitor in human diseases has been recognized, recombinant techniques have also been employed for the production of human CFH in Physcomitrella patens [33], Pichia pastoris [34] and a baculovirus system [35], which provided biologically active human CFH but low yields of 3–5 mg/l of fermentation supernatant [35,36] as compared to concentrations approximately 50 times higher found in intermediates of industrial plasma fractionation.…”

Section: Discussionmentioning

confidence: 99%

“…Human plasma is a rich source of CFH; hence, industrial fractionation intermediates are an obvious source to develop a CFH concentrate for intravenous application. A number of purification processes have been reported by other working groups in order to obtain purified CFH preparations from human, rat or mouse plasma [20–26]. However, the described methods were intended to purify CFH for analytical and research purposes on a laboratory scale only and are essentially less suitable for an industrial‐scale process, including the required steps regarding pathogen safety.…”

Section: Introductionmentioning

confidence: 99%

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