Fibrin and Extracellular Matrix: Scaffolds and Network for Malignant Cells
Main Article Content
Abstract
Malignant cells build up a protective shield in form of a fibrin meshwork surrounding the tumor which helps it to escape the body’s immune system. In addition, tumor and stromal cells provide with an abundant extracellular matrix (ECM) consisting of proteoglycans, collagens, glycoproteins and glucosaminoglycans an additional scaffold with the capacity to bind large quantities of immunsuppressive substances. Many investigations found that heparin has a wide variety of positive effects counteracting these shielding and immunosuppressive properties of the ECM. Heparin can bind and neutralize many protective substances produced by the tumor cells. It inhibits cross-linking of collagen by deamination, and reduces the expression of FAK, LOX, glucosamines and proteoglycans. By these actions it prevents the development of a stiff and rigid ECM which presents additionally an effective scaffold for the tumor cells and also reduce the efficiency of therapeutic methods. In an ambulant trial with exogenously-added heparin in high dosages the survival probability over three years was significantly higher than without (p<0.001). Therefore, a combined therapy with a fibrinolyticum and heparin should be considered. This auxiliary treatment has the potential to support established therapy and improve anti-tumor response by the immune system.
Keywords:
fibrin, heparin, FAK, LOX, glucosamine, proteoglycans
Article Details
How to Cite
SCHARDT, F.W. et al.
Fibrin and Extracellular Matrix: Scaffolds and Network for Malignant Cells.
Medical Research Archives, [S.l.], v. 9, n. 9, sep. 2021.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2551>. Date accessed: 26 apr. 2024.
doi: https://doi.org/10.18103/mra.v9i9.2551.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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4. Falanga A. The effect of anticoagulant drugs on cancer. Thromb Haemost. 2004; 2:1263-65
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6. Schardt FW, Schmausser B, Bachmann E. Monoclonal antibodies for immunodetection of fibrin deposits on cancer cells. Histol Histopathol. 2013; 28: 993-998
7. Hill AB. Principles of medical statistics. Lancet. 1966;34-38
8. Benjamin D, Mandel DR, Kimmelmann J. Can cancer researchers accurately judge whether preclinical reports will reproduce? PLoS Biol. 2017; 15:6
9. Wojtukiewicz MZ, Rucinska M, Zacharski LR, et al. Localization of blood coagulation factors in situ in pancreatic carcinoma. Thromb Haemost.2001;86:1416-20
10. Gieseler F, Lühr I, Kunze T. Activated coagulation factors in human malignant effusions and their contribution to cancer cell metastasis and therapy. Thromb Haemost. 2007;97:1023-30
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12. Tang L, Han X. The urokinase plasminogen activator system in breast cancer invasion and metasis. Biomed Pharmacotherapy. 2013;67,2,:179-18212.
13. Zacharski LR. Heparin treatment of malignancy: the case for clinical trials in colon cancer. Thromb Res. 2003;110,4:213-214
14. Laner-Plamberger S, Oeller M, Poupardin R, et.al. Heparin differentially impacts gene expression of stroma from various tissues. Nature Sci Rep. 2019;9:728-7302
15. Barbouri D, Afratis N, Gialeli C, et al. Syndecans as modulators and potential pharmagological targets in cancer progression. Front Oncol. 2014;4:4-11
16. Furukawa K, Bhavanandan VP. Influences of anionic polysaccharides on DNA synthesis in isolated nuclei and by polymerase alpha: correlation of observed effects with properties of the polysaccharides. Biochim Biophys Acta. 1983;9,740,4:466-475
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38. Zhao D, Plotnikoff N, Griffin N, et al. Methionine enkephalin, its role in immunoregulation and cancer therapy. Int Immunopharmacol. 2016;37:59-64
39. Pasternak GW. Multiple Morphine and Enkephalin Receptors and the Relief of Pain. JAMA. 1988;259,9:1362-1369
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