Fibronectin concentration in plasma of patients with breast cancer, colon cancer, and acute leukemia

Choate, Jennifer J.; Mosher, Deane F.

doi:10.1002/1097-0142(19830315)51:6<1142::aid-cncr2820510628>3.0.co;2-s

Cited by 68 publications

(24 citation statements)

References 17 publications

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“…For example, some cancer patients who have received chemotherapy have low fibronectin levels (36). An antiangiogenic protein that depends on plasma fibronectin for its activity could be less effective in patients with low fibronectin levels.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic proteins require plasma fibronectin or vitronectin for in vivo activity

Sakai

Fässler

et al. 2003

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

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Fragmentation of various extracellular matrix and blood proteins generates antiangiogenic substances that are physiological regulators of angiogenesis. Some of these compounds are in clinical trials as inhibitors of tumor angiogenesis. Anastellin, an antiangiogenic protein fragment derived from fibronectin, was unable to inhibit matrigel plug angiogenesis in mice that lack plasma fibronectin. Anastellin was fully active in mice that are null for vitronectin, which, like fibronectin, is a major adhesion protein in the blood. An antiangiogenic form of antithrombin showed the opposite pattern. The activity of endostatin was impaired in both fibronectin-and vitronectin-deficient mice. These results suggest a shared mechanism of action for antiangiogenic factors derived from extracellular matrix and plasma proteins: these factors form complexes with adhesion proteins in plasma to create an active antiangiogenic substance.A growing class of antiangiogenic substances is derived from extracellular matrix and blood proteins by proteolysis or other modifications. These substances include fragments from thrombospondin (1), plasminogen (angiostatin; ref. (5), and the fibronectin fragment anastellin (6, 7). The molecular mechanisms whereby these substances exert their antiangiogenic activities are poorly understood. Anastellin binds to and polymerizes fibronectin and fibrinogen (8, 9). The antiangiogenic form of antithrombin is similar to the modified antithrombin that binds vitronectin (10, 11). Vitronectin, like fibronectin, is an arginine-glycine-aspartic acid (RGD)-containing adhesion protein present in plasma (12). Other angiogenesis inhibitors also interact with one or more adhesion proteins: angiostatin and its parent protein, plasminogen, bind vitronectin (13), whereas endostatin binds fibulins and nidogen-2 (14).The interactions of the various angiogenesis inhibitors with adhesion proteins led us to hypothesize that adhesion protein binding could underlie antiangiogenic activity, and that activities of the various inhibitors could converge on this ability to form such adhesion protein complexes (7). To test this hypothesis, we examined the two antiangiogenic proteins with the most extensively documented adhesion protein interactions, anastellin and antithrombin. We used angiogenesis induced by implanting matrigel (basement membrane) plugs (15, 16) into mutant mice that conditionally lack plasma fibronectin (17) or have their vitronectin gene knocked out (18).We show here that anastellin does not suppress angiogenesis in matrigel plugs implanted into mice that lack plasma fibronectin. In contrast, the antiangiogenic form of antithrombin is inactive in mice that lack vitronectin. Endostatin is essentially inactive in mice that lack either plasma fibronectin or vitronectin. These results strongly support the hypothesis that the activity of extracellular matrix-and blood protein-derived angiogenesis inhibitors depends on interactions with adhesion proteins. Materials and MethodsProteins. Anastellin (a fragment from the...

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Section: Discussionmentioning

confidence: 99%

Antiangiogenic proteins require plasma fibronectin or vitronectin for in vivo activity

Sakai

Fässler

et al. 2003

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

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“…The results have been contradictory. High plasma levels of total FN have been reported in patients with breast, ovarian, lung, pancreatic and colonic carcinoma (Mosher and Williams, 1978;Parsons et al, 1979a,b;Todd et al, 1980;Choate and Mosher, 1983), whereas reduced levels of FN have been reported in plasma of patients with lymphatic leukaemia (Bruhn and Heimburger, 1976) and haemopathic diseases (De Russe et al, 1985). Interestingly, the latter diseases differ from carcinomas in that they lack a stromal response.…”

Section: Discussionmentioning

confidence: 99%

“…Determining the concentration of FN in plasma appears useful in evaluating the status of the mononuclear phagocytic system (Mosher, 1980;Stathakis et al, 1981). In many studies total FN in plasma and other body fluids has been evaluated as a marker for cancer or other diseases (Parsons et al, 1979a,b;Webb and Linn, 1980;Stathakis et al, 1981;Choate and Mosher, 1983;Siri et al, 1984;Boccardo et al, 1986;Ruelland et al, 1988;Katayama et al, 1991). For this purpose various quantitative methods for measuring FN concentration have been developed.…”

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confidence: 99%

Cellular fibronectin in serum and plasma: a potential new tumour marker?

Ylätupa¹,

Haglund²,

Mertaniemi³

et al. 1995

Br J Cancer

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Summary The concentration of cellular fibronectin (cFN) containing the extra domain A (EDA) was measured in 479 plasma and 300 serum samples from healthy blood donors by a competitive enzyme immunoassay (EIA). Serum and plasma samples contained low concentrations of EDAcFN. The mean concentration of EDAcFN was higher in plasma (2.46mgl-') than in serum (0.30mg1-'). No significant differences between sexes or age groups were found. The EDAcFN concentrations were also measured in 120 patients with various malignancies.

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“…The corresponding sensitivities for digestive tract malignancies were 69%, 42% and 58% respectively; and the specificities, based on benign digestive tract diseases, were 73%, 83% and 81% respectively (Table 3). (Humphries et al, 1988;Schwarzbauer, 1991 (Mosher and Williams, 1978;Parsons et al, 1979a,b;Todd et al, 1980;Choate and Mosher, 1983), whereas normal FN concentrations have been reported in patients with leukaemia (Bruhn and Heimburger, 1976;Choate and Mosher, 1983). On the other hand, Eijan et al (1986) did not find elevated total FN levels in breast cancer, and increased plasma concentrations of total FN levels may also be found in various benign conditions (Todd et al, 1980).…”

Section: Edacfn In Plasma Of Patients With Benign Diseasesmentioning

confidence: 99%

“…In many studies, total FN in plasma and other body fluids has been evaluated as a marker for cancer or other diseases (Parsons et al, 1979a,b;Webb and Linn, 1980;Stathakis et al, 1981;Choate and Mosher, 1983;Siri et al, 1984;Boccardo et al, 1986;Ruelland et al, 1988; Katayama et al, 1991). Only recently have specific antibodies made it possible to study the cellular form of FN containing the EDA sequence (EDAcFN).…”

mentioning

confidence: 99%

Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: a comparison with CA 19-9 and CEA

Haglund

Ylätupa²,

Mertaniemi³

et al. 1997

Br J Cancer

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Summary EDAcFN enzyme immunoassay (EIA) is a new tumour marker assay measuring the extra domain A-containing isoform of cellular fibronectin (cFN), a component mainly found in extracellular matrices. The concentration cFN was measured in plasma and serum from 468 patients with malignant and benign diseases. The concentrations of cFN were higher in plasma than in serum. Using receiver operating characteristic (ROC) curve analysis, determination from plasma was superior to serum at specificity levels higher than 78% and was chosen for further analysis. The highest frequencies of elevated cFN values were seen in patients with hepato-pancreato-biliary malignancies (50-67%). In pancreatic and bile duct cancers, cFN provided little further information to that obtained by CA 19-9. The greatest advantage over CA 19-9 and CEA was seen in patients with local colorectal cancer and in hepatocellular carcinomas. Four out of nine patients with Dukes' stage B colorectal cancer had an elevated cFn level, but only one had an abnormal CEA level. In hepatocellular carcinomas, cFN was also compared with alpha-fetoprotein. The sensitivity of cFN (72%) was superior to that of AFP (61%), and concomitant use of cFN and AFP raised the sensitivity to 83%. The highest frequencies of elevated values in patients with benign diseases were observed in those with severe liver disease (32%) and biliary (17%) and pancreatic (24%) diseases. A combination of cFN and CA showed the highest overall sensitivity of 47%, compared with 31% for cFN and 33% for CA 19-9. The corresponding specificities were 76% for cFN ± CA 19-9, 85% for cFN and 83% for CA 19-9. The accuracy of a combination of cFN and CA 19-9 or CEA (60% respectively) was higher than that of cFN (55%), CA 19-9 (55%) or CEA (45%) alone. In conclusion, the results of the new cFN test are encouraging and further studies on larger patient materials have been started.

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Fibronectin concentration in plasma of patients with breast cancer, colon cancer, and acute leukemia

Cited by 68 publications

References 17 publications

Antiangiogenic proteins require plasma fibronectin or vitronectin for in vivo activity

Antiangiogenic proteins require plasma fibronectin or vitronectin for in vivo activity

Cellular fibronectin in serum and plasma: a potential new tumour marker?

Cellular fibronectin concentration in the plasma of patients with malignant and benign diseases: a comparison with CA 19-9 and CEA

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