Role of fibrinolysis and α2-macroglobulin in growth of primary adenocarcinoma and rectal polyps.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15093-e15093
Author(s):  
Evgeniy N. Kolesnikov ◽  
Elena Alekseevna Nikipelova ◽  
Elena Mikhaylovna Frantsiyants ◽  
Larisa Kozlova ◽  
Irina V. Kaplieva ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Protective Effect ◽  
Tumor Angiogenesis ◽  
Active Form ◽  
Primary Adenocarcinoma ◽  
Α2 Macroglobulin ◽  
Rectal Polyps ◽  
Resection Line

e15093 Background: An important role in tumor angiogenesis induction is played by hydrolytic systems, in particular plasmin one which provides degradation of the extracellular matrix, activates growth factors and metalloproteinases. Our purpose was to analyze the tissue fibrinolytic system and α2-macroglobulin (α2M) in primary adenocarcinoma (PA) and polyps (P) of the rectum (R). Methods: Tissues of tumors (РА, G2, T2-3N0M0, 42-73 years) and their perifocal zone (PZ) in R (n = 24) and Р (n = 27) were studied by ELISA; the result was calculated per 1 mg of tissue. Results: Resection line (RL) tissues contained levels of tРА antigen and its active form (tРА-Ag and tРА-act) 6.7 and 33.8 times higher than prourokinase and urokinase levels (uPA-Ag and uPA-act). RL tissues in P did not differ significantly from R tissues at PA resection. uPA-act in PA was higher than in RL by 3.2 times, uPA-Ag - 8 times higher, tРА-act - 2.3 times lower; tPA-Ag was similar to RL tissue values. Plasmin-α2-antiplasmin complex (PAP) in PA was 1.4 times higher than in RL. Plasminogen (PG) in PA was 1.5 times lower than in RL (p < 0.01). Activity of α2M in PA and RL did not differ. PAP and α2М in PA PZ were similar to RL, and PG did not differ from PA. Other indices were between tumor and RL levels. P tissue did not show changes in uPA; tPA-act activity was 1.3 times lower than in RL, and tPA-Ag 1.3 times higher (p < 0.01). PAP in tissues of 88.2% P was 1.5 times higher than in RL and 1.7 times lower than in PA. PG and α2М were similar in P and RL. PAP in PZ of P was 2.3 times higher than in RL and 1.5 times higher than in PA PZ. PG in P PZ was 1.4 times lower than in RL (p < 0.01). α2М activity in P PZ was higher than in RL and P by 5.4 times on average. uPA in P PZ did not differ from RL; tРА-Ag and tРА-act were higher than in RL by 1.5 and 1.9 times and exceeded P by 2.1 and 1.5 times (p < 0.01). Prevalence of uPA, activation of PG in PA and its PZ indicated degradation of the extracellular matrix compared with the corresponding P tissues. Conclusions: The role of R tumor PZ as a "metabolic" tumor field in neoplasm progression was confirmed. Activation of fibrinolysis in PA and its PZ with a deficiency of inhibitors stimulates the migration and proliferation of cells. Increasing tРА, РАР and α2М in PZ of polyps has a protective effect.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

scholarly journals Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 409 ◽  
Author(s):  
Manuela Antoniel ◽  
Francesco Traina ◽  
Luciano Merlini ◽  
Davide Andrenacci ◽  
Domenico Tigani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Critical Role ◽  
Active Form ◽  
Congenital Muscular Dystrophy ◽  
Cell Polarization ◽  
Pcr Analysis ◽  
Matrix Remodeling ◽  
Collagen Vi

Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.

THE PROTECTIVE EFFECT OF ACYLATI0N ON THE STABILITY OF EMINASE (APSAC) IN HUMAN PLASMA

1987 ◽  
Author(s):  
R Fears ◽  
H Ferres ◽  
R Standring
Keyword(s):  
Protective Effect ◽  
Human Plasma ◽  
Fibrinolytic Activity ◽  
Animal Studies ◽  
Active Form ◽  
Α2 Macroglobulin ◽  
The Stability ◽  
High Level ◽  
Activator Complex

Clinical and animal studies indicate that APSAC (anisoylated plasminogen.streptokinase activator complex, Eminase) circulates longer in the bloodstream in an active form than the other thrombolytics. In the present studies in vitro u/e have found that functional activity of APSAC is maintained in human plasma longer than that of SK.plasmin(ogen): the relative stability half-lives are similar to the plasma clearance haif-lives in patients. Some of the loss of activity of SK at early times can be attributed to neutralisation by inhibitors. Thus, the survival of fibrinolytically-active SK was promoted in plasma depleted in α2-antiplasmin (α2AP) and α2AP-SK.plasmin complexes (detected by immunoblotting) formed rapidly in normal plasma. Corresponding studies with α2 macroglobulin-depleted plasma suggested a slight, late influence on SK activity but the inhibitor complex has not been detected unequivocally. In addition, loss of SK activity can be attributed, in part, to. rapid degradation to low molecular products. The degradation of SK in APSAC was much slower. In other comparative studies, the stability of APSAC was found to be similar to the stability of prourokinase and much superior to that of SK which is similar to UK; t-PA is intermediate in stability.Maintenance of fibrinolytic activity vivo depends on the stability of the thrombolytic, its rate of clearance and mode of administration. The protective effect of acylation, demonstrated in these experiments, explains why the objective of maintaining a high level of fibrinolytic activity after intravenous bolus injection of APSAC is less compromised by opposing inactivation processes.

scholarly journals Role of extracellular matrix, growth factors and proto-oncogenes in metanephric development

1997 ◽  
Vol 52 (3) ◽  
pp. 589-606 ◽  
Author(s):  
Yashpal S. Kanwar ◽  
Frank A. Carone ◽  
Anil Kumar ◽  
Jun Wada ◽  
Kosuke Ota ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors

Pathophysiological Mechanisms Destruction of the Lung Connective Tissue in Tuberculosis

2019 ◽  
pp. 14-20
Author(s):  
O. S. Shevchenko ◽  
I. A. Ovcharenko ◽  
L. D. Todoriko
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Collagen Fibers ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Blood Monocytes ◽  
Pulmonary Tissue ◽  
Α2 Macroglobulin ◽  
The Family ◽  
Pathological Event

Background. The restructuring of the lung tissue stroma during destructive tuberculosis is one of the most important pathological events in the formation of residual changes in the lung tissue during tuberculosis inflammation. Most patients with tuberculosis have destructive forms of this disease. Therefore, studies of pathomorphological changes in the pulmonary tissue of tuberculosispatients are very relevant. It is known that the formation of decavities in volves the destruction of the extracellular matrix, which includes collagen fibers that support the structure of the lungs. The destruction of this matrix leads to the destruction of lung tissue and is a consequence of the activity of proteinase enzymes. One of the products of the destruction of collagen fibers of the lung tissue is oxyproline and its fractions. It has been proventhatin the lungs collagen fibers break down matrix metalloproteinases (MMPs), which belong to the family of proteinases, and are able to affectall component soft he extracellular matrix. The process of MMP synthesis is regulated at the transcription level, and the irproteolytic activity is controlled by proenzymes, as well as inhibition of active enzymes by endogenous inhibitors, α2-macroglobulin and tissue inhibitors of metalloproteinases (TIMP), which play an important role in fibrosis processes. However, it is important not only the level of MMP, but also their ratio with TIMP. An increase in the level of TIMP over MMP leads to the degradation of capillaries of the interalveolar septa, while the predominance of MMP over TIMP leads to the destruction of the component soft he extracellular matrix. Recent studies indicate the role of aldosterone in the processes of fibrosis. It is able to activate blood monocytes, induce in flammation, lead to impaired fibrinolysis. Also aldosterone is able to enhance the synthesis and accumulation of collagen. Elevated levels of aldosterone, stimulating the growth of smooth muscle fibers, contribute to the development of fibrosis in the lungs. There is evidence that aldosterone is able to enhance the degradation of the extracellular matrix through the activation of MMP. Conclusions. Thus, the destruction of the extracellular matrixis one of the most important pathological event sin the formation of residual changes in the lung tissue with tuberculous inflammation.

ROLE OF GROWTH FACTORS ON EXTRACELLULAR MATRIX PRODUCTION BY CHICK EMBRYO FIBROBLASTS IN VITRO. ANTAGONIST EFFECT OF TGF-β THROUGH THE CONTROL OF IL-1 AND IL-1Ra SECRETION

Cytokine ◽  
1998 ◽  
Vol 10 (5) ◽  
pp. 353-360 ◽  
Author(s):  
Maria Bodo ◽  
Paolo Carinci ◽  
Tiziano Baroni ◽  
Catia Bellucci ◽  
Monica Giammarioli ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Chick Embryo ◽  
Extracellular Matrix Production ◽  
Matrix Production ◽  
Embryo Fibroblasts ◽  
Antagonist Effect
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