Members of the plasminogen-plasmin (PP) system participate in many physiologic functions. In particular, uPA, its receptor (uPAR) and its inhibitor PAI-1 play an important role in cell migration, cell proliferation and tissue remodeling. Through a number of interactions, these components of the PP system are also involved in the pathogenesis of many diseases. In cancer, they modulate the essential processes of tumor development, growth, invasion and metastasis as well as angiogenesis and fibrosis. Thus, quantification of uPA, uPAR and PAI-1 in tumors and, in some cases in the circulating blood, became of potential value in the prognostication of many types of cancer. These include cancer of the breast, stomach, colon and rectum, esophagus, pancreas, glioma, lung, kidney, prostate, uterine cervix, ovary, liver and bone. Published data are reviewed in this chapter. Clinical validation of the prognostic value has also been made, particularly in cancer of the breast. Inclusion of these biomarkers in the risk assessment of cancer patients is now considered in the risk-adapted management in carcinoma of the breast. Factors limiting its broader use are discussed with suggestions how these can be overcome. Hopefully the use of these biomarkers will be applied to other types of cancer in the near future.
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http://dx.doi.org/10.1007/978-94-017-7215-0_10 | DOI Listing |
Nat Commun
November 2024
Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the host-pathogen protein-protein interaction between plasminogen and streptolysin O, a key cytolytic toxin produced by GAS. This interaction accelerates the conversion of plasminogen to plasmin by both the host tissue-type plasminogen activator and streptokinase, a bacterial plasminogen activator secreted by GAS.
View Article and Find Full Text PDFOral Dis
July 2024
The State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Sichuan, China.
Biochem Pharmacol
July 2024
Grupo de Reprodução e Farmacologia Celular, Laboratório de Bioquímica Farmacológica, Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA-UFRGS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências de Saúde: Ginecologia e Obstetrícia (PPGGO), Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address:
The pivotal role of human endometrial stromal cells (hESCs) in the development of endometriosis lies in their ability to adopt a pro-invasive and proinflammatory profile upon migration to areas outside the uterus. However, the molecular mechanisms involved in these events remain unclear. In this study, we investigated how angiotensin II (Ang II) affects the plasminogen-plasmin system in hESCs, and the mechanisms underlying cell proliferation, migration, matrix degradation, and inflammation.
View Article and Find Full Text PDFJCI Insight
March 2024
Division of Immunology & Rheumatology, Stanford School of Medicine, Stanford, California, USA.
Cardiovasc Diabetol
February 2024
Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, 28029, Madrid, Spain.
Early since the onset of the COVID-19 pandemic, the medical and scientific community were aware of extra respiratory actions of SARS-CoV-2 infection. Endothelitis, hypercoagulation, and hypofibrinolysis were identified in COVID-19 patients as subsequent responses of endothelial dysfunction. Activation of the endothelial barrier may increase the severity of the disease and contribute to long-COVID syndrome and post-COVID sequelae.
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