123
Views
8
CrossRef citations to date
0
Altmetric
Review

Aberrant Factors of Fibrinolysis and Coagulation in Pancreatic Cancer

, , & ORCID Icon
Pages 53-65 | Published online: 06 Jan 2021

References

  • Henley SJ, Ward EM, Scott S, et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2020;126(10):2225–2249. doi:10.1002/cncr.32802
  • Drouillard A, Manfredi S, Lepage C, Bouvier A-M. [Epidemiology of pancreatic cancer]. Bull Cancer. 2018;105(1):63–69. French. doi:10.1016/j.bulcan.2017.11.004
  • Donnellan E, Khorana AA. Cancer and venous thromboembolic disease: a review. Oncologist. 2017;22(2):199–207. doi:10.1634/theoncologist.2016-0214
  • Hisada Y, Mackman N. Cancer-associated pathways and biomarkers of venous thrombosis. Blood. 2017;130(13):1499–1506. doi:10.1182/blood-2017-03-743211
  • Sgouros J, Maraveyas A. Excess premature (3-month) mortality in advanced pancreatic cancer could be related to fatal vascular thromboembolic events. A hypothesis based on a systematic review of Phase III chemotherapy studies in advanced pancreatic cancer. Acta Oncol (Madr). 2008. doi:10.1080/02841860701687267
  • Kruger S, Haas M, Burkl C, et al. Incidence, outcome and risk stratification tools for venous thromboembolism in advanced pancreatic cancer - a retrospective cohort study. Thromb Res. 2017;157:9–15. doi:10.1016/j.thromres.2017.06.021
  • Lyman GH, Bohlke K, Khorana AA, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014. J Clin Oncol. 2015;33(6):654–656. doi:10.1200/JCO.2014.59.7351
  • Cao J, Fu Z, Gao L, et al. Evaluation of serum D-dimer, fibrinogen, and CA19-9 for postoperative monitoring and survival prediction in resectable pancreatic carcinoma. World J Surg Oncol. 2017;1–8. doi:10.1186/s12957-017-1104-9
  • Kulic A, Cvetkovic Z, Libek V. Primary hyperfibrinolysis as the presenting sign of prostate cancer: a case report. Vojnosanit Pregl. 2016;73(9):877–880. doi:10.2298/VSP150525076K
  • Jafri MA, Cohen JV, Much MA, Petrylak DP, Podoltsev NA, Patient With A. Pancytopenia, intractable epistaxis, and metastatic prostate cancer: how correct diagnosis of primary hyperfibrinolysis helps to stop the bleeding. Clin Genitourin Cancer. 2016;14(5):e545–e548. doi:10.1016/j.clgc.2016.05.002
  • Naina HVK, Patnaik MM, Ali UA, Chen D, Ashrani AA. Systemic fibrinolysis caused by tissue plasminogen activator-producing metastatic breast cancer. J Clin Oncol. 2010;28(11):e167–e168. doi:10.1200/JCO.2009.25.2502
  • Baluka D, Urbanek T, Lekstan A, et al. The role of the tissue plasminogen activator as a prognostic and differentiation factor in patients with pancreatic cancer and chronic pancreatitis. J Physiol Pharmacol. 2016;67(1):93–101.
  • Huang C, Xie D, Cui J, Li Q, Gao Y, Xie K. FOXM1c promotes pancreatic cancer epithelial-to-mesenchymal transition and metastasis via upregulation of expression of the urokinase plasminogen activator system. Clin Cancer Res. 2014;20(6):1477–1488. doi:10.1158/1078-0432.CCR-13-2311
  • McMahon BJ, Kwaan HC. Components of the plasminogen-plasmin system as biologic markers for cancer. Adv Exp Med Biol. 2015;867:145–156.
  • Chen Q, Fei J, Wu L, et al. Detection of cathepsin B, cathepsin L, cystatin C, urokinase plasminogen activator and urokinase plasminogen activator receptor in the sera of lung cancer patients. Oncol Lett. 2011;2(4):693–699. doi:10.3892/ol.2011.302
  • Rubina KA, Sysoeva VY, Zagorujko EI, et al. Increased expression of uPA, uPAR, and PAI-1 in psoriatic skin and in basal cell carcinomas. Arch Dermatol Res. 2017;309(6):433–442. doi:10.1007/s00403-017-1738-z
  • Yang SF, Hsieh YS, Lin CL, et al. Increased plasma levels of urokinase plasminogen activator and matrix metalloproteinase-9 in nonsmall cell lung cancer patients. Clin Chim Acta. 2005;354(1–2):91–99. doi:10.1016/j.cccn.2004.11.011
  • Urban P, Vuaroqueaux V, Labuhn M, et al. Increased expression of urokinase-type plasminogen activator mRNA determines adverse prognosis in ErbB2-positive primary breast cancer. J Clin Oncol. 2006;24(26):4245–4253. doi:10.1200/JCO.2005.05.1912
  • Halamkova J, Kiss I, Pavlovsky Z, et al. Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients. Neoplasma. 2011;58(5):377–385. doi:10.4149/neo_2011_05_377
  • Liu Q, Li W, Yang S, Liu Z. High expression of uPA related to p38MAPK in esophageal cancer indicates poor prognosis. Onco Targets Ther. 2018;11:8427–8434. doi:10.2147/OTT.S181701
  • Ma J, Qi G, Xu J, et al. Overexpression of forkhead box M1 and urokinase-type plasminogen activator in gastric cancer is associated with cancer progression and poor prognosis. Oncol Lett. 2017;14(6):7288–7296. doi:10.3892/ol.2017.7136
  • Wang X, Wang N, Li H, et al. Up-regulation of PAI-1 and down-regulation of uPA are involved in suppression of invasiveness and motility of hepatocellular carcinoma cells by a natural compound berberine. Int J Mol Sci. 2016;17(4):577. doi:10.3390/ijms17040577
  • Kumano M, Miyake H, Muramaki M, Furukawa J, Takenaka A, Fujisawa M. Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol. 2009;27(2):180–186. doi:10.1016/j.urolonc.2008.01.012
  • Taubert H, Wurl P, Greither T, et al. Co-detection of members of the urokinase plasminogen activator system in tumour tissue and serum correlates with a poor prognosis for soft-tissue sarcoma patients. Br J Cancer. 2010;102(4):731–737. doi:10.1038/sj.bjc.6605520
  • Pavon MA, Arroyo-Solera I, Cespedes MV, Casanova I, Leon X, Mangues R. uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy. Oncotarget. 2016;7(35):57351–57366. doi:10.18632/oncotarget.10344
  • Nielsen A, Scarlett CJ, Samra JS, et al. Significant overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma using real-time quantitative reverse transcription polymerase chain reaction. J Gastroenterol Hepatol. 2005;20:256–263. doi:10.1111/j.1400-1746.2004.03531.x
  • Shin SJ, Kim KO, Kim MK, et al. Expression of E-cadherin and uPA and their association with the prognosis of pancreatic cancer. Japan J Clin Oncol. 2005;35(6):342–348. doi:10.1093/jjco/hyi094
  • Wang W, Abbruzzese JL, Evans DB, Chiao PJ. Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA. Oncogene. 1999;18(32):4554–4563. doi:10.1038/sj.onc.1202833
  • Harvey SR, Hurd TC, Markus G, et al. Evaluation of urinary plasminogen activator, its receptor, matrix metalloproteinase-9, and von Willebrand factor in pancreatic cancer. Clin Cancer Res. 2003;9(13):4935–4943.
  • Gibbs JF, Schlieman M, Singh P, et al. A pilot study of urokinase-type plasminogen activator (uPA) overexpression in the brush cytology of patients with malignant pancreatic or biliary strictures. HPB Surg. 2009;2009:1–5. doi:10.1155/2009/805971
  • Takeuchi Y, Nakao A, Harada A, Nonami T, Fukatsu T, Takagi H. Expression of plasminogen activators and their inhibitors in human pancreatic carcinoma: immunohistochemical study. Am J Gastroenterol. 1993;88(11):1928–1933.
  • Boss EA, Massuger LFAG, Thomas CMG, et al. Clinical value of components of the plasminogen activation system in ovarian cyst fluid. Anticancer Res. 2002;22(1A):275–282.
  • Shim BS, Kang BH, Hong YK, et al. The kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth. Biochem Biophys Res Commun. 2005;327(4):1155–1162. doi:10.1016/j.bbrc.2004.12.126
  • Grebenchtchikov N, Maguire TM, Riisbro R, et al. Measurement of plasminogen activator system components in plasma and tumor tissue extracts obtained from patients with breast cancer: an EORTC Receptor and Biomarker Group collaboration. Oncol Rep. 2005;14(1):235–239.
  • Sciacca FL, Ciusani E, Silvani A, et al. Genetic and plasma markers of venous thromboembolism in patients with high grade glioma. Clin Cancer Res. 2004;10(4):1312–1317. doi:10.1158/1078-0432.ccr-03-0198
  • De Petro G, Tavian D, Copeta A, Portolani N, Giulini SM, Barlati S. Expression of urokinase-type plasminogen activator (u-PA), u-PA receptor, and tissue-type PA messenger RNAs in human hepatocellular carcinoma. Cancer Res. 1998;58(10):2234–2239.
  • Wojtukiewicz MZ, Sierko E, Zacharski LR, Rózanska-Kudelska M, Zimnoch L. Occurrence of components of fibrinolytic pathways in situ in laryngeal cancer. Semin Thromb Hemost. 2003;29(3):317–320. doi:10.1055/s-2003-40970
  • Collen D, Lijnen HR. The tissue-type plasminogen activator story. Arterioscler Thromb Vasc Biol. 2009;29(8):1151–1155. doi:10.1161/ATVBAHA.108.179655
  • Marignol L, Robson T, McCarthy HO, et al. The tissue plasminogen activator gene promoter: a novel tool for radiogenic gene therapy of the prostate? J Gene Med. 2008;10(9):1032–1038. doi:10.1002/jgm.1221
  • Sanz L, Vizoso F, Vérez P, et al. Prognostic significance of tissue-type plasminogen activator (tPA) content in gastric cancer and surrounding mucosa. Int J Biol Markers. 2002;17(3):169–176. doi:10.1177/172460080201700305
  • Neudecker J, Neudecker BA, Raue W, Stern R, Schwenk W. Hyaluronan levels during laparoscopic versus open colonic resections. Surg Endosc. 2008;22(3):660–663. doi:10.1007/s00464-007-9455-x
  • Chappuis PO, Dieterich B, Sciretta V, et al. Functional evaluation of plasmin formation in primary breast cancer. J Clin Oncol. 2001;19(10):2731–2738. doi:10.1200/JCO.2001.19.10.2731
  • Corte MD, Vérez P, Rodríguez JC, et al. Tissue-type plasminogen activator (tPA) in breast cancer: relationship with clinicopathological parameters and prognostic significance. Breast Cancer Res Treat. 2005;90(1):33–40. doi:10.1007/s10549-004-2624-x
  • Diaz VM, Planaguma J, Thomson TM, Reventos J, Paciucci R. Tissue plasminogen activator is required for the growth, invasion, and angiogenesis of pancreatic tumor cells. Gastroenterology. 2002;122(3):806–819. doi:10.1053/gast.2002.31885
  • Diaz VM, Hurtado M, Thomson TM, Reventos J, Paciucci R. Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro. Gut. 2004;53(7):993–1000. doi:10.1136/gut.2003.026831
  • Nielsen VG, Matika RW, Ley MLB, et al. Tissue-type plasminogen activator-induced fibrinolysis is enhanced in patients with breast, lung, pancreas and colon cancer. Blood Coagul Fibrinolysis. 2014;25(3):248–253. doi:10.1097/MBC.0000000000000040
  • Gao F, Li J, Quan S, et al. Risk factors and treatment for hemorrhage after pancreaticoduodenectomy: a case series of 423 patients. Biomed Res Int. 2016;2016:2815693. doi:10.1155/2016/2815693
  • Uramoto H, Shimokawa H, Tanaka F. Postoperative bleeding after surgery in patients with lung cancer. Anticancer Res. 2014;34(2):981–984.
  • Deryugina EI, Quigley JP. Cell surface remodeling by plasmin: a new function for an old enzyme. J Biomed Biotechnol. 2012;2012:564259. doi:10.1155/2012/564259
  • Kwaan HC, Mazar AP, McMahon BJ. The apparent uPA/PAI-1 paradox in cancer: more than meets the eye. Semin Thromb Hemost. 2013;39(4):382–391. doi:10.1055/s-0033-1338127
  • Kwaan HC, McMahon B. The role of plasminogen-plasmin system in cancer. Cancer Treat Res. 2009;148:43–66. doi:10.1007/978-0-387-79962-9_4
  • Houard X, Monnot C, Dive V, Corvol P, Pagano M. Vascular smooth muscle cells efficiently activate a new proteinase cascade involving plasminogen and fibronectin. J Cell Biochem. 2003;88(6):1188–1201. doi:10.1002/jcb.10460
  • Diao D, Cheng Y, Song Y, Zhang H, Zhou Z, Dang C. D-dimer is an essential accompaniment of circulating tumor cells in gastric cancer. BMC Cancer. 2017;17(1):56. doi:10.1186/s12885-016-3043-1
  • Mego M, Zuo Z, Gao H, et al. Circulating tumour cells are linked to plasma D-dimer levels in patients with metastatic breast cancer. Thromb Haemost. 2015;113(3):593–598. doi:10.1160/TH14-07-0597
  • Mego M, Karaba M, Minarik G, et al. Relationship between circulating tumor cells, blood coagulation, and urokinase-plasminogen-activator system in early breast cancer patients. Breast J. 2015;21(2):155–160. doi:10.1111/tbj.12388
  • Stender MT, Larsen AC, Sall M, Thorlacius-Ussing O. D-dimer predicts prognosis and non-resectability in patients with pancreatic cancer: a prospective cohort study. Blood Coagul Fibrinolysis. 2016;27(5):597–601. doi:10.1097/MBC.0000000000000559
  • Vishwanatha JK, Chiang Y, Kumble KD, Hollingsworth MA, Pour PM. Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis. 1993;14(12):2575–2579. doi:10.1093/carcin/14.12.2575
  • Cesarman GM, Guevara CA, Hajjar KA. An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem. 1994;269(33):21198–21203.
  • Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem. 1994;269(33):21191–21197.
  • Sidenius N, Blasi F. The urokinase plasminogen activator system in cancer: recent advances and implication for prognosis and therapy. Cancer Metastasis Rev. 2003;22(2–3):205–222. doi:10.1023/a:1023099415940
  • Gorantla B, Asuthkar S, Rao JS, Patel J, Gondi CS. Suppression of the uPAR-uPA system retards angiogenesis, invasion, and in vivo tumor development in pancreatic cancer cells. Mol Cancer Res. 2011;9(4):377–389. doi:10.1158/1541-7786.MCR-10-0452
  • DiPardo BJ, Winograd P, Court CM, Tomlinson JS. Pancreatic cancer circulating tumor cells: applications for personalized oncology. Expert Rev Mol Diagn. 2018;18(9):809–820. doi:10.1080/14737159.2018.1511429
  • Zwicker JI, Furie BC, Furie B. Cancer-associated thrombosis. Crit Rev Oncol Hematol. 2007;62(2):126–136. doi:10.1016/j.critrevonc.2007.01.001
  • Vannucchi AM, Barbui T. Thrombocytosis and thrombosis. Hematology Am Soc Hematol Educ Program. 2007;2007:363–370. doi:10.1182/asheducation-2007.1.363
  • Hwang SG, Kim KM, Cheong JH, et al. Impact of pretreatment thrombocytosis on blood-borne metastasis and prognosis of gastric cancer. Eur J Surg Oncol. 2012;38(7):562–567. doi:10.1016/j.ejso.2012.04.009
  • Pedersen LM, Milman N. Prognostic significance of thrombocytosis in patients with primary lung cancer. Eur Respir J. 1996;9(9):1826–1830. doi:10.1183/09031936.96.09091826
  • Cravioto-Villanueva A, Luna-Perez P, Gutierrez-de la Barrera M, et al. Thrombocytosis as a predictor of distant recurrence in patients with rectal cancer. Arch Med Res. 2012;43(4):305–311. doi:10.1016/j.arcmed.2012.06.008
  • Zhu J-F, Cai L, Zhang X-W, et al. High plasma fibrinogen concentration and platelet count unfavorably impact survival in non-small cell lung cancer patients with brain metastases. Chin J Cancer. 2014;33(2):96–104. doi:10.5732/cjc.012.10307
  • Yamamoto M, Kurokawa Y, Miyazaki Y, et al. Usefulness of preoperative plasma fibrinogen versus other prognostic markers for predicting gastric cancer recurrence. World J Surg. 2016;40(8):1904–1909. doi:10.1007/s00268-016-3474-5
  • Fan S, Guan Y, Zhao G, An G. Association between plasma fibrinogen and survival in patients with small-cell lung carcinoma. Thorac Cancer. 2018;9(1):146–151. doi:10.1111/1759-7714.12556
  • Man Y-N, Wang Y-N, Hao J, et al. Pretreatment plasma D-dimer, fibrinogen, and platelet levels significantly impact prognosis in patients with epithelial ovarian cancer independently of venous thromboembolism. Int J Gynecol Cancer. 2015;25(1):24–32. doi:10.1097/IGC.0000000000000303
  • Erdem S, Amasyali AS, Aytac O, Onem K, Issever H, Sanli O. Increased preoperative levels of plasma fibrinogen and D dimer in patients with renal cell carcinoma is associated with poor survival and adverse tumor characteristics. Urol Oncol. 2014;32(7):1031–1040. doi:10.1016/j.urolonc.2014.03.013
  • Wang H, Gao J, Bai M, et al. The pretreatment platelet and plasma fibrinogen level correlate with tumor progression and metastasis in patients with pancreatic cancer. Platelets. 2014;25(5):382–387. doi:10.3109/09537104.2013.827782
  • Liu P, Zhu Y, Liu L. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma. Onco Targets Ther. 2015;8:1335–1340. doi:10.2147/OTT.S82329
  • Guo Q, Zhang B, Dong X, et al. Elevated levels of plasma fibrinogen in patients with pancreatic cancer: possible role of a distant metastasis predictor. Pancreas. 2009;38(3):e75–e79. doi:10.1097/MPA.0b013e3181987d86
  • Kurahara H, Maemura K, Mataki Y, et al. Prognostication by inflammation-based score in patients with locally advanced pancreatic cancer treated with chemoradiotherapy. Pancreatology. 2015;15(6):688–693. doi:10.1016/j.pan.2015.09.015
  • Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med. 2000;6(1):100–102. doi:10.1038/71429
  • Jurk K, Kehrel BE. Platelets: physiology and biochemistry. Semin Thromb Hemost. 2005;31(4):381–392. doi:10.1055/s-2005-916671
  • Jackson SP. Arterial thrombosis–insidious, unpredictable and deadly. Nat Med. 2011;17(11):1423–1436. doi:10.1038/nm.2515
  • Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer. 2011;11(2):123–134. doi:10.1038/nrc3004
  • Karpatkin S, Pearlstein E, Ambrogio C, Coller BS. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest. 1988;81(4):1012–1019. doi:10.1172/JCI113411
  • Jain S, Zuka M, Liu J, et al. Platelet glycoprotein Ib alpha supports experimental lung metastasis. Proc Natl Acad Sci U S A. 2007;104(21):9024–9028. doi:10.1073/pnas.0700625104
  • Jain S, Russell S, Ware J. Platelet glycoprotein VI facilitates experimental lung metastasis in syngenic mouse models. J Thromb Haemost. 2009;7(10):1713–1717. doi:10.1111/j.1538-7836.2009.03559.x
  • Kim YJ, Borsig L, Varki NM, Varki A. P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci U S A. 1998;95(16):9325–9330. doi:10.1073/pnas.95.16.9325
  • Chen M, Geng JG. P-selectin mediates adhesion of leukocytes, platelets, and cancer cells in inflammation, thrombosis, and cancer growth and metastasis. Arch Immunol Ther Exp (Warsz). 2006;54(2):75–84. doi:10.1007/s00005-006-0010-6
  • Wei M, Tai G, Gao Y, et al. Modified heparin inhibits P-selectin-mediated cell adhesion of human colon carcinoma cells to immobilized platelets under dynamic flow conditions. J Biol Chem. 2004;279(28):29202–29210. doi:10.1074/jbc.M312951200
  • McCarty OJ, Mousa SA, Bray PF, Konstantopoulos K. Immobilized platelets support human colon carcinoma cell tethering, rolling, and firm adhesion under dynamic flow conditions. Blood. 2000;96(5):1789–1797. doi:10.1182/blood.V96.5.1789
  • Varga-Szabo D, Pleines I, Nieswandt B. Cell adhesion mechanisms in platelets. Arterioscler Thromb Vasc Biol. 2008;28(3):403–412. doi:10.1161/ATVBAHA.107.150474
  • Da Q, Behymer M, Correa JI, Vijayan KV, Cruz MA. Platelet adhesion involves a novel interaction between vimentin and von Willebrand factor under high shear stress. Blood. 2014;123(17):2715–2721. doi:10.1182/blood-2013-10-530428
  • Hong S-H, Misek DE, Wang H, et al. Identification of a specific vimentin isoform that induces an antibody response in pancreatic cancer. Biomark Insights. 2006;1:175–183. doi:10.1177/117727190600100006
  • Palumbo JS, Talmage KE, Massari JV, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood. 2005;105(1):178–185. doi:10.1182/blood-2004-06-2272
  • Palumbo JS, Degen JL. Fibrinogen and tumor cell metastasis. Haemostasis. 2001;31 Suppl 1(Suppl 1):11–15.
  • Palumbo JS, Potter JM, Kaplan LS, Talmage K, Jackson DG, Degen JL. Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res. 2002;62(23):6966–6972.
  • Tsakadze NL, Zhao Z, D’Souza SE. Interactions of intercellular adhesion molecule-1 with fibrinogen. Trends Cardiovasc Med. 2002;12(3):101–108. doi:10.1016/S1050-1738(01)00157-8
  • Roland CL, Dineen SP, Toombs JE, et al. Tumor-derived intercellular adhesion molecule-1 mediates tumor-associated leukocyte infiltration in orthotopic pancreatic xenografts. Exp Biol Med (Maywood). 2010;235(2):263–270. doi:10.1258/ebm.2009.009215
  • Tempia-Caliera AA, Horvath LZ, Zimmermann A, et al. Adhesion molecules in human pancreatic cancer. J Surg Oncol. 2002;79(2):93–100. doi:10.1002/jso.10053
  • Shimoyama S, Gansauge F, Gansauge S, Kaminishi M, Beger HG. Basal expression and cytokine induction of intercellular adhesion molecule-1 in human pancreatic cancer cell lines. J Exp Clin Cancer Res. 1999;18(1):107–110.
  • Weyrich AS, Zimmerman GA. Platelets: signaling cells in the immune continuum. Trends Immunol. 2004;25(9):489–495. doi:10.1016/j.it.2004.07.003
  • Lam FW, Vijayan KV, Rumbaut RE. Platelets and their interactions with other immune cells. Compr Physiol. 2015;5(3):1265–1280. doi:10.1002/cphy.c140074
  • Kopp H-G, Placke T, Salih HR. Platelet-derived transforming growth factor-beta down-regulates NKG2D thereby inhibiting natural killer cell antitumor reactivity. Cancer Res. 2009;69(19):7775–7783. doi:10.1158/0008-5472.CAN-09-2123
  • Placke T, Örgel M, Schaller M, et al. Platelet-derived MHC class I confers a pseudonormal phenotype to cancer cells that subverts the antitumor reactivity of natural killer immune cells. Cancer Res. 2012;72(2):440–448. doi:10.1158/0008-5472.CAN-11-1872
  • Placke T, Kopp H-G, Salih HR. Modulation of natural killer cell anti-tumor reactivity by platelets. J Innate Immun. 2011;3(4):374–382. doi:10.1159/000323936
  • Rachidi S, Metelli A, Riesenberg B, et al. Platelets subvert T cell immunity against cancer via GARP-TGFβ axis. Sci Immunol. 2017;2(11):eaai7911. doi:10.1126/sciimmunol.aai7911
  • Maugeri N, Campana L, Gavina M, et al. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost. 2014;12(12):2074–2088. doi:10.1111/jth.12710
  • Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013;123(8):3446–3458. doi:10.1172/JCI67484
  • Boone BA, Orlichenko L, Schapiro NE, et al. The receptor for advanced glycation end products (RAGE) enhances autophagy and neutrophil extracellular traps in pancreatic cancer. Cancer Gene Ther. 2015;22(6):326–334. doi:10.1038/cgt.2015.21
  • Ahrens I, Chen Y-C, Topcic D, et al. HMGB1 binds to activated platelets via the receptor for advanced glycation end products and is present in platelet rich human coronary artery thrombi. Thromb Haemost. 2015;114(11):994–1003. doi:10.1160/TH14-12-1073
  • Chung HW, Lim J-B, Jang S, Lee KJ, Park KH, Song SY. Serum high mobility group box-1 is a powerful diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma. Cancer Sci. 2012;103(9):1714–1721. doi:10.1111/j.1349-7006.2012.02358.x
  • Wittwer C, Boeck S, Heinemann V, et al. Circulating nucleosomes and immunogenic cell death markers HMGB1, sRAGE and DNAse in patients with advanced pancreatic cancer undergoing chemotherapy. Int J Cancer. 2013;133(11):2619–2630. doi:10.1002/ijc.28294
  • Zheng S, Shen J, Jiao Y, et al. Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci. 2009;100(5):859–865. doi:10.1111/j.1349-7006.2009.01115.x
  • Mastoraki A, Mastoraki S, Schizas D, et al. Facing the challenge of venous thromboembolism prevention in patients undergoing major abdominal surgical procedures for gastrointestinal cancer. World J Gastrointest Oncol. 2018;10(10):328–335. doi:10.4251/wjgo.v10.i10.328
  • Camerer E, Qazi AA, Duong DN, Cornelissen I, Advincula R, Coughlin SR. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood. 2004;104(2):397–401. doi:10.1182/blood-2004-02-0434
  • Amirkhosravi A, Mousa SA, Amaya M, et al. Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thromb Haemost. 2003;90(09):549–554. doi:10.1160/TH03-02-0102
  • Zhang W, Dang S, Hong T, et al. A humanized single-chain antibody against beta 3 integrin inhibits pulmonary metastasis by preferentially fragmenting activated platelets in the tumor microenvironment. Blood. 2012;120(14):2889–2898. doi:10.1182/blood-2012-04-425207
  • Bakewell SJ, Nestor P, Prasad S, et al. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A. 2003;100(24):14205–14210. doi:10.1073/pnas.2234372100
  • Erpenbeck L, Nieswandt B, Schön M, Pozgajova M, Schön MP. Inhibition of platelet GPIb alpha and promotion of melanoma metastasis. J Invest Dermatol. 2010;130(2):576–586. doi:10.1038/jid.2009.278
  • Lavergne M, Janus-Bell E, Schaff M, Gachet C, Mangin PH. Platelet integrins in tumor metastasis: do they represent a therapeutic target? Cancers (Basel). 2017;9(10):133. doi:10.3390/cancers9100133
  • Qi C-L, Wei B, Ye J, et al. P-selectin-mediated platelet adhesion promotes the metastasis of murine melanoma cells. PLoS One. 2014;9(3):e91320. doi:10.1371/journal.pone.0091320
  • Qi C, Wei B, Zhou W, et al. P-selectin-mediated platelet adhesion promotes tumor growth. Oncotarget. 2015;6(9):6584–6596. doi:10.18632/oncotarget.3164
  • Xu XR, Yousef GM, Ni H. Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents. Blood. 2018;131(16):1777–1789.
  • Zelenay S, van der Veen AG, Böttcher JP, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell. 2015;162(6):1257–1270. doi:10.1016/j.cell.2015.08.015
  • Alsubaie H, Leggett C, Lambert P, et al. Diagnosis of VTE postdischarge for major abdominal and pelvic oncologic surgery: implications for a change in practice. Can J Surg. 2015;58(5):305–311. doi:10.1503/cjs.012314
  • Cui G, Wang X, Yao W, Li H. Incidence of postoperative venous thromboembolism after laparoscopic versus open colorectal cancer surgery: a meta-analysis. Surg Laparosc Endosc Percutan Tech. 2013;23(2):128–134. doi:10.1097/SLE.0b013e3182827cef
  • Cheung HY, Chung CC, Yau KK, et al. Risk of deep vein thrombosis following laparoscopic rectosigmoid cancer resection in chinese patients. Asian J Surg. 2008;31(2):63–68. doi:10.1016/S1015-9584(08)60060-3
  • Gil-Bernabé AM, Lucotti S, Muschel RJ. Coagulation and metastasis: what does the experimental literature tell us? Br J Haematol. 2013;162(4):433–441. doi:10.1111/bjh.12381
  • Cuzick J, Thorat MA, Bosetti C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2015;26(1):47–57. doi:10.1093/annonc/mdu225
  • Jiang M-J, Dai -J-J, Gu D-N, Huang Q, Tian L. Aspirin in pancreatic cancer: chemopreventive effects and therapeutic potentials. Biochim Biophys Acta. 2016;1866(2):163–176. doi:10.1016/j.bbcan.2016.08.002
  • Streicher SA, Yu H, Lu L, Kidd MS, Risch HA. Case-control study of aspirin use and risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1254–1263. doi:10.1158/1055-9965.EPI-13-1284
  • Risch HA, Lu L, Streicher SA, et al. Aspirin use and reduced risk of pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2017;26(1):68–74. doi:10.1158/1055-9965.EPI-16-0508
  • Cui X-J, He Q, Zhang J-M, Fan H-J, Wen Z-F, Qin Y-R. High-dose aspirin consumption contributes to decreased risk for pancreatic cancer in a systematic review and meta-analysis. Pancreas. 2014;43(1):135–140. doi:10.1097/MPA.0b013e3182a8d41f
  • Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA. 1995;273(20):1605–1609. doi:10.1001/jama.1995.03520440059037
  • Yue W, Yang CS, DiPaola RS, Tan X-L. Repurposing of metformin and aspirin by targeting AMPK-mTOR and inflammation for pancreatic cancer prevention and treatment. Cancer Prev Res (Phila). 2014;7(4):388–397. doi:10.1158/1940-6207.CAPR-13-0337
  • Yue W, Zheng X, Lin Y, et al. Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2. Oncotarget. 2015;6(25):21208–21224. doi:10.18632/oncotarget.4126
  • Mezouar S, Darbousset R, Dignat-George F, Panicot-Dubois L, Dubois C. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo. Int J Cancer. 2015;136(2):462–475. doi:10.1002/ijc.28997
  • Mitrugno A, Sylman JL, Ngo ATP, et al. Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: implications for the oncoprotein c-MYC. Am J Physiol Cell Physiol. 2017;312(2):C176–C189. doi:10.1152/ajpcell.00196.2016
  • Chen H, Lan X, Liu M, Zhou B, Wang B, Chen P. Direct TGF-β1 signaling between activated platelets and pancreatic cancer cells primes cisplatin insensitivity. Cell Biol Int. 2013;37(5):478–484. doi:10.1002/cbin.10067
  • Green D, Hull RD, Brant R, Pineo GF. Lower mortality in cancer patients treated with low-molecular-weight versus standard heparin. Lancet (London, England). 1992;339(8807):1476. doi:10.1016/0140-6736(92)92064-m
  • Wahrenbrock M, Borsig L, Le D, Varki N, Varki A. Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas. J Clin Invest. 2003;112(6):853–862. doi:10.1172/JCI18882
  • Klerk CPW, Smorenburg SM, Otten H-M, et al. The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol. 2005;23(10):2130–2135. doi:10.1200/JCO.2005.03.134
  • Mousa SA, Mohamed S. Inhibition of endothelial cell tube formation by the low molecular weight heparin, tinzaparin, is mediated by tissue factor pathway inhibitor. Thromb Haemost. 2004;92(09):627–633. doi:10.1160/TH04-02-0069
  • Stevenson JL, Varki A, Borsig L. Heparin attenuates metastasis mainly due to inhibition of P- and L-selectin, but non-anticoagulant heparins can have additional effects. Thromb Res. 2007;120(Suppl):S107–s111. doi:10.1016/S0049-3848(07)70138-X
  • Borsig L, Wong R, Feramisco J, Nadeau DR, Varki NM, Varki A. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A. 2001;98(6):3352–3357. doi:10.1073/pnas.061615598
  • Yoshitomi Y, Nakanishi H, Kusano Y, et al. Inhibition of experimental lung metastases of Lewis lung carcinoma cells by chemically modified heparin with reduced anticoagulant activity. Cancer Lett. 2004;207(2):165–174. doi:10.1016/j.canlet.2003.11.037
  • Maraveyas A, Ettelaie C, Echrish H, et al. Weight-adjusted dalteparin for prevention of vascular thromboembolism in advanced pancreatic cancer patients decreases serum tissue factor and serum-mediated induction of cancer cell invasion. Blood Coagul Fibrinolysis. 2010;21(5):452–458. doi:10.1097/MBC.0b013e328338dc49
  • Sudha T, Yalcin M, Lin H-Y, et al. Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin. Cancer Lett. 2014;350(1–2):25–33. doi:10.1016/j.canlet.2014.04.016
  • Sudha T, Phillips P, Kanaan C, Linhardt RJ, Borsig L, Mousa SA. Inhibitory effect of non-anticoagulant heparin (S-NACH) on pancreatic cancer cell adhesion and metastasis in human umbilical cord vessel segment and in mouse model. Clin Exp Metastasis. 2012;29(5):431–439. doi:10.1007/s10585-012-9461-9
  • Agnelli G, Gussoni G, Bianchini C, et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol. 2009;10(10):943–949. doi:10.1016/S1470-2045(09)70232-3
  • von Delius S, Ayvaz M, Wagenpfeil S, Eckel F, Schmid RM, Lersch C. Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma. Thromb Haemost. 2007;98(08):434–439. doi:10.1160/TH07-01-0004
  • Icli F, Akbulut H, Utkan G, et al. Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer. J Surg Oncol. 2007;95(6):507–512. doi:10.1002/jso.20728
  • Pelzer U, Opitz B, Deutschinoff G, et al. Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 trial. J Clin Oncol. 2015;33(18):2028–2034. doi:10.1200/JCO.2014.55.1481
  • Sideras K, Schaefer PL, Okuno SH, et al. Low-molecular-weight heparin in patients with advanced cancer: a Phase 3 clinical trial. Mayo Clin Proc. 2006;81(6):758–767. doi:10.4065/81.6.758
  • Di Nisio M, Porreca E, Candeloro M, De Tursi M, Russi I, Rutjes AW. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2016;12(12):CD008500. doi:10.1002/14651858.CD008500.pub4