{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:57:30Z","timestamp":1793840250842,"version":"4.6.1"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    The primary role of the fibrinolytic system is to degrade fibrin clots. However, the fibrinolytic system is often activated in patients with cancer and may affect cancer progression, metastasis, and patient survival. Clinical studies have shown that elevated plasma levels of uPA (urokinase plasminogen activator) are associated with cancer progression in patients with prostate, bladder, and cervical cancers, whereas high plasma levels of soluble uPAR (uPA receptor) are associated with progression and metastasis in prostate, breast, bladder, and colorectal cancers. Elevated levels of plasmin-\u03b1\n                    <jats:sub>2<\/jats:sub>\n                    -antiplasmin complexes, a marker of activation of the fibrinolytic system, have been linked to reduced survival in patients with soft tissue sarcoma, lung, and metastatic breast cancers. Studies with mouse models have shown that uPA, uPAR, tPA (tissue-type plasminogen activator), and plasmin contribute to tumor growth, metastasis, and survival. For instance, uPA and uPAR can activate kinase signaling pathways in cancer cells, whereas tPA can activate LRP1 (lipoprotein receptor\u2013related protein 1), which enhances tumor growth and metastasis. Plasmin can degrade the extracellular matrix, which would increase cancer cell migration. In addition, it can release extracellular matrix\u2013bound growth factors, which could increase tumor growth and angiogenesis. Taken together, these studies suggest that the fibrinolytic system promotes cancer progression and metastasis through multiple mechanisms.\n                  <\/jats:p>","DOI":"10.1161\/atvbaha.124.321603","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T09:00:17Z","timestamp":1756976417000},"page":"1732-1741","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Profibrinolytic Factors and Cancer Progression, Metastasis, and Survival"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9157-0524","authenticated-orcid":true,"given":"Yohei","family":"Hisada","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-7700","authenticated-orcid":true,"given":"Nigel","family":"Mackman","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, UNC Blood Research Center, University of North Carolina at Chapel Hill."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14157"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.12.039"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH13-06-0517"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2014.09.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000570"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)52382-6"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpth.2023.100081"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008951"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1159\/000051082"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0006OC"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.12.7224"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32252"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers9040035"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1327107"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.11.010"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80429-8"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297-439"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030361"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.4.672"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/84635"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205342"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801339RRR"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4863"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64637-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2007.00554.x"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00199509"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1159\/000204586"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-4295(02)02522-0"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000001936"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1538-7836.2003.00207.x"},{"key":"e_1_3_3_33_2","first-page":"252","article-title":"Increased plasma levels of urokinase-type plasminogen activator with endometrial and cervical cancer.","volume":"72","author":"Koelbl H","year":"1988","unstructured":"Koelbl H, Kirchheimer JC, Tatra G, Christ G, Binder BR. 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