Occurrence of Components of Fibrinolytic Pathways in Situ in Laryngeal Cancer

Marek Z. Wojtukiewicz; Ewa Sierko; Leo R. Zacharski; Malgorzata Rózanska-Kudelska; Lech Zimnoch

doi:10.1055/s-2003-40970

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2003; 29(3): 317-320
DOI: 10.1055/s-2003-40970

Occurrence of Components of Fibrinolytic Pathways in Situ in Laryngeal Cancer

Marek Z. Wojtukiewicz¹ , Ewa Sierko² , Leo R. Zacharski³ , Malgorzata Rózanska-Kudelska⁴ , Lech Zimnoch⁵

¹Professor of Medicine and Oncology, Department of Oncology, Medical Academy, Bialystok, Poland
²Department of Oncology, Medical Academy, Bialystok, Poland
³Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire and the Department of Veterans Affairs Medical and Regional Office Center, White River Junction, Vermont
⁴Department of Otolaryngology, Medical Academy, Bialystok, Poland
⁵Department of Pathomorphology, Medical Academy, Bialystok, Poland

Abstract

ABSTRACT

Malignancy is characterized by the occurrence of components of coagulation reaction pathways in situ within tumor tissues detectable immunohistochemically. However, tumors vary in the details of this coagulation-cancer interaction. We have previously described tumor cell-associated tissue factor (TF), factor (F) VII, and F X in laryngeal carcinoma tissues. Fibrinogen and F XIIIa were found in the tumor connective tissue. Tissue factor pathway inhibitor (TFPI) occurred in the tumor connective tissue and on microvascular endothelial cells and normal squamous epithelial cells but not in the tumor cells. Fibrin (thrombin-cleaved fibrinogen) existed at the host-tumor interface and the margins of tumor nodules consistent with an active tumor cell-associated clotting pathway in this tumor type. Studies were extended here to detect components of fibrinolytic pathways. Plasminogen and tissue plasminogen activator (t-PA) were detected on laryngeal tumor cells, particularly in more well-differentiated cases. Low-molecular-weight urokinase plasminogen activator (LMW u-PA) was primarily a feature of more undifferentiated laryngeal carcinoma cells. Staining to a lesser extent was found for high-molecular-weight u-PA (HMW u-PA) on tumor cells and various normal cell types in the tumor tissue. Relatively weak and variable tumor cell staining was found for plasminogen activator inhibitors (PAI) 1, 2, and 3. Trace staining was found for u-PA receptor (u-PAR) in differentiated tumor cells. The significance of coagulation and fibrinolytic pathways present in situ to the economy of laryngeal carcinoma remains to be determined.

KEYWORDS

Laryngeal cancer - blood coagulation - fibrinolysis

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References

REFERENCES

1 Francis J L, Biggerstaff J, Amirkhosravi A. Hemostasis and malignancy. Semin Thromb Hemost . 1998; 24 93-109
2 Bromberg M E, Capello M. Cancer and blood coagulation: molecular aspects. Cancer J . 1999; 5 132-138
3 Wojtukiewicz M Z, Rucinska M, Zimnoch L. et al . Expression of prothrombin fragment 1+2 in cancer tissue as an indicator of local activation of blood coagulation. Thromb Res . 2000; 97 335-342
4 Wojtukiewicz M Z, Zacharski L R, Memoli V A. et al . Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma of the lung. Cancer . 1990; 65 481-485
5 Wojtukiewicz M Z, Zacharski L R, Memoli V A. et al . Malignant melanoma. Interaction with coagulation and fibrinolysis pathways in situ. Am J Clin Pathol . 1990; 93 516-521
6 Wojtukiewicz M Z, Zacharski L R, Memoli V A. et al . Fibrinogen-fibrin transformation in situ in renal cell carcinoma. Anticancer Res . 1990; 10 579-582
7 Wojtukiewicz M Z, Zacharski L R, Rucinska M. et al . Expression of tissue factor and tissue factor pathway inhibitor in situ in laryngeal carcinoma. Thromb Haemost . 1999; 82 1659-1662
8 Wojtukiewicz M Z, Rucinska M, Zacharski L R. et al . Localization of blood coagulation factors in situ in pancreatic carcinoma. Thromb Haemost . 2001; 86 1416-1420
9 Zacharski L R, Wojtukiewicz M Z, Costantini V, Ornstein D L, Memoli V A. Pathways of coagulation/fibrinolysis activation in malignancy. Semin Thromb Hemost . 1992; 18 104-116
10 Constantini V, Zacharski L R, Memoli V A. et al . Occurence of components of fibrinolysis pathways in situ in neoplasmatic human breast tissue. Cancer Res . 1991; 51 354-358
11 Ornstein D L, Constantini V, Zacharski L R. et al . Coexistent macrophage procoagulant and tumor cell plasminogen activator in adenocarcinoma and squamous cell carcinoma of the lung. Cancer . 1991; 68 1061-1067
12 Wojtukiewicz M Z, Zacharski L R, Memoli V A. et al . Indirect activation of blood coagulation in colon cancer. Thromb Haemost . 1989; 62 1062-1066
13 Wojtukiewicz M Z, Zacharski L R, Memoli V A. et al . Fibrin formation on vessel walls in hyperplastic and malignant prostate tissue. Cancer . 1991; 67 1377-1383
14 Nasyrov V A, Osmonowa R O, Rachkol A G. State of the hemostasis system in patients with malignant III-stage neoplasms of the maxilla and larynx. Vestn Otorinolaringol . 1991; 5 12-15
15 Sato Y, Mukai K, Watanabe S, Goto M, Shimosato Y. The AMeX method. The simplified technique of tissue processing and paraffin embedding with improved preservation of antigens for immunostaining. Am J Pathol . 1986; 125 431-435
16 Hsu S, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem . 1981; 29 577-580
17 Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost . 1999; 82 259-270
18 Wojtukiewicz M Z, Sierko E, Klement P, Rak J. The hemostatic system and angiogenesis in neoplasms. Neoplasia . 2001; 51 93-103
19 Carroll V A, Binder B R. The role of the plasminogen activation system in cancer. Semin Thromb Haemost . 1999; 25 183-197
20 Lentschener C, Li H, Franco D. et al . Intraoperatively-administered aprotinin and survival after elective liver resection for colorectal cancer metastasis. A preliminary study. Fibrinolysis Proteolysis . 1999; 13 39-45
21 Zacharski L R, Ornstein D L. Heparin and cancer. Thromb Haemost . 1998; 80 10-23
22 Pasini F, Brentani M M, Kowalski L P, Federico M H. Transforming growth factor-1, urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in head and neck squamous carcinoma and normal adjacent mucosa. Head Neck . 2001; 23 725-732
23 Parolini S. Flagiello D, Cinquetti A, et al. Up-regulation of urokinase-type plasminogen activator in squamous cell carcinoma of human larynx. Br J Cancer . 1996; 74 1168-1174
24 Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K. Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer . 1996; 78 487-492
25 Pyke C, Kristensen P, Ralfkiaer E. et al . Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol . 1991; 138 1059-1067
26 Bianchi E, Cohen R L, Thor A T. et al . The urokinase receptor is expressed in invasive breast cancer but not in normal breast tissue. Cancer Res . 1994; 54 861-866
27 De Vries J T, Quax P HA, Denijn M. et al . Plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of melanocytic tumor progression. Am J Pathol . 1994; 144 70-81
28 Pedersen H, Grondahl-Hansen J, Francis D. et al . Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma. Cancer Res . 1994; 54 120-123
29 Cohen R L, Xi X-P, Crowley C W. et al . Effects of urokinase receptor occupancy on plasmin generation and proteolysis of basement membrane by human tumor cells. Blood . 1991; 78 479-487
30 Blasi F. Proteolysis, cell adhesion, chemotaxis, and invasiveness are regulated by the u-PA-u-PAR-PAI-1 system. Thromb Haemost . 1999; 82 298-304
31 Homer J J, Greenman J, Stafford N D. The expression of vascular endothelial growth factor (VEGF) and VEGF-C in early laryngeal cancer: relationship with radioresistance. Clin Otolaryngol . 2001; 26 498-504