Indirect Activation of Blood Coagulation in Colon Cancer

Marek Z Wojtukiewicz; Leo R Zacharski; Vincent A Memoli; Walter Kisiel; Bohdan J Kudryk; Sandra M Rousseau; David C Stump

doi:10.1055/s-0038-1647118

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 62(04): 1062-1066
DOI: 10.1055/s-0038-1647118

Original Article

Coagulation

Schattauer GmbH Stuttgart

Indirect Activation of Blood Coagulation in Colon Cancer

Authors

Marek Z Wojtukiewicz

¹The Department of Medicine, Dartmouth Medical School, Vermont, USA

³The VA Medical Center, White River Junction, Vermont, USA
Leo R Zacharski

¹The Department of Medicine, Dartmouth Medical School, Vermont, USA

³The VA Medical Center, White River Junction, Vermont, USA
Vincent A Memoli

²The Department of Pathology, Dartmouth Medical School, Vermont, USA
Walter Kisiel

⁴The Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico
Bohdan J Kudryk

⁵The Plasma Protein-Coagulation Laboratory, New York Blood Center, New York, New York
Sandra M Rousseau

³The VA Medical Center, White River Junction, Vermont, USA
David C Stump

⁶The Departments of Medicine and Biochemistry, University of Vermont Medical School, Burlington, Vermont, USA

Abstract

PDF Download

Summary

Systemic activation of the coagulation mechanism is known to exist in patients with colon cancer. The mechanism of such activation was investigated using immunohistochemical techniques applied to fresh frozen sections of resected primary colon cancer specimens. Tumor cells stained for tissue factor, factor V, and urokinase-type plasminogen activator. Perivascular and intercellular areas stained for fibrinogen and the “a” subunit of factor XIII. Staining was minimal or absent for protein C, protein S, plasminogen activator inhibitors 1-3, factor VII, factor X, and fibrin (the antigenic site on the amino-terminal portion of Bβ chain that is exposed following thrombin cleavage of fibrinopeptide B was not detected). The lack of an intact thrombin- generating pathway in situ associated with viable colon cancer cells is consistent with the findings of others that coagulation activation in colon cancer may be triggered by a soluble tumor product that exerts its effect at sites distant from the tumor. These results may explain the absence of clinical responsiveness of colon cancer to antithrombotic drug therapy and may clarify therapeutic strategies for this common tumor.

Keywords

Blood coagulation - Colon cancer

PDF (268 kb)

References

References
1 Miller SP, Sanchez-Avalos J, Stefanski T, Zuckerman L. Coagulation disorders in cancer. i. Clinical and laboratory studies. Cancer 1967; 20: 1452-1465
2 Mitchell WH, Parson BJ, Althous J. Coagulation problems in patients with cancer. J Surg Oncol 1980; 13: 323-327
3 Slichter SJ, Harker LA. Hemostasis and malignancy. Ann NY Acad Sci 1974; 230: 252-261
4 Soong B CF, Miller SP. Coagulation disorders in cancer. Cancer 1970; 25: 867-874
5 Sun N CJ, Bowie E JW, Kazmire F, Elvebach LR, Owen CA. Blood coagulation studies in patients with cancer. Mayo Clin Proc 1974; 49: 636-641
6 Sun N CJ, McAfee WM, Hum GJ, Weiner JM. Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Am J Clin Pathol 1979; 71: 10-16
7 Peuscher FW, Cleton FJ, Armstrong L, Stoepman-van Dalen EA, van Mourik JA, van Aken WG. Significance of plasma fibrinopeptide A (fpA) in patients with malignancy. J Lab Clin Med 1980; 96: 5-14
8 Rickles FR, Edwards RL, Barb C, Cronlund M. Abnormalities of blood coagulation in patients with cancer. Fibrinopeptide A generation and tumor growth Cancer 1983; 51: 301-307
9 Abbasciano V, Zevato F, Zavagli G. Specificity of fibrinopeptide A (fpA) as a marker for gastrointestinal cancers before and after surgery. Med Oncol Tumor Pharmacother 1987; 4: 75-79
10 Carlsson S. Fibrinogen degradation products in serum from patients with cancer. Acta Chir Scand 1973; 139: 499-502
11 Williams CK O, Pineo GF, Gallus AS, McCulloch PB. The relevance of platelet and fibrinogen kinetics and coagulation studies to extent of disease and performance status in patients with adenocarcinoma. Med Pediat Oncol 1980; 8: 367-374
12 Sharma PV P, Babu SC, Shah PM, Seirafi R, Clauss RH. Arterial thrombosis and embolism in malignancy. J Cardiovasc Surg 1985; 26: 479-483
13 Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1983; 62: 14-31
14 Ambrus JL, Ambrus CM, Pickern J, Soldes S, Bross I. Hematologic changes and thromboembolic complications in neoplastic disease and their relationship to metastasis. J Med 1976; 6: 433-458
15 Berkheiser SW. Pulmonary intra-arteriolar thrombi associated with cancer. Cancer 1958; 11: 99-105
16 Gore JM, Appelbaum JS, Greene HL, Dexter L, Dalen JE. Occult cancer in patients with acute pulmonary embolism. Ann Intern Med 1982; 96: 556-560
17 Donati MB, Poggi A, Semeraro N. Coagulation and malignancy. In: Recent Advances in Blood Coagulation, Vol. 3. Poller L. (ed) Livingston; New York: 1981: 375-391
18 Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell Jr CJ, Forcier RJ, Headley E, Kim S-H, O-Donnell FJ, O’Dell RJ, Tornyos K, Kwaan HC. Effect of sodium warfarin on survival in small cell carcinoma of the lung. JAMA 1981; 245: 831-835
19 Chahinian AP, Ware JH, Zimmer B, Comis RL, Perry MC, Hirsh V, Skarin AT, Raich PC, Weiss RB, Green M, Carrey RW. Update on anticoagulation with warfarin and on alternating chemotherapy in extensive small cell carcinoma of the lung (SCCL). Proc Am Soc Clin Oncol 1985; 4: 191
20 Zacharski LR, Moritz TE, Baczek LA, Rickles FR, Edwards RL, Forman WG, Forcier RJ, Cornell CJ, Haakenson CM, Ballard HS, Crum ED, Johnson GJ, Levine J, Hong WK, O’Donnell JF, Schilsky RL, Ringenberg QS, Robert F, Spaulding MB, Tornyos K, William C, Zucker S. Effect of RA-233 (Mopidamole) on survival in carcinoma of the lung and colon. Final report of VA Cooperative Study No. 188 J Natl Cancer Inst 1988; 80: 90-97
21 Schneider B, Geser C, Feuerer W. Effect of anticoagulant treatment with RA-233 (Mopidamole) on survival in bronchial cancer. Thromb Haemostas 1987; 58: 508 (Abstr)
22 Zacharski LR, Henderson WG, Rickles FR, Forman WB, Cornell CJ, Forcier RJ, Edwards RL, Headley E, Kim S-H, O’Donnell JF, O-Dell R, Tornyos K, Kwaan HC. Effect of warfarin anticoagulation on survival in carcinoma of the lung, colon, head and neck, and prostate. Final report of VA Cooperative Study No. 75 Cancer 1984; 53: 2046-2052
23 Lipton A, Scialla S, Harvey H, Dixon R, Gordon R, Hamilton R, Ramsey H, Weltz M, Heckard R, White D. Adjuvant antiplatelet therapy with aspirin in colorectal cancer. J Med 1083; 13: 419-429
24 Daly L. Personal communication. 1988
25 Torngren S, Rieger A. The influence of heparin and curable resection on the survival of colorectal cancer. Acta Chir Scand 1983; 149: 427-429
26 Harvey H, Lipton A, Dixon R, Gordon R, Walker B, Bartholomew M, Heckard R. Adjuvant antiplatelet therapy of colo-rectal cancer. Proc ASCO 1987; 6: 79
27 Wojtukiewicz MZ, Zacharski LR, Memoli VA, Wojtukiewicz MZ, Kisiel W, Kudryk B, Rousseau SM, Stump DC, Wilcox J. Abnormal regulation of coagulation/fibrinolysis in small cell carcinoma of the lung. Cancer 1990 (in press)
28 Zacharski LR, Memoli VA, Rousseau SM, Kisiel W. Coagulationcancer interaction in situ in small cell carcinoma of the lung. Cancer 1987; 60: 2675-2681
29 Zacharski LR, Memoli VA, Rousseau SM. Thrombin-specific sites of fibrinogen in small cell carcinoma of the lung. Cancer 1988; 62: 299-302
30 Zacharski LR, Memoli VA, Rousseau SM. Cancer-coagulation interaction in situ in renal cell carcinoma. Blood 1986; 68: 394-399
31 Zacharski LR, Schned A, Sorenson GD. Occurrence of fibrin and tissue factor antigen in small cell carcinoma of the lung. Cancer Res 1983; 43: 3963-3968
32 Paborsky LR, Tate KM, Harris RJ, Yansura D, Band L, McCray G, Gorman CM, O’Brien Dp, Chang JY, Swartz JR, Fung VP, Thomas JN, Vehar GA. Purification of recombinant human tissue factor. Biochem 1989; 28: 8072-8077
33 Stump DC, Thienpont M, Collen D. Urokinase-related proteins in human urine. Isolation and characterization of single-chain urokinase (pro-urokinase) and urokinase-inhibitor complex J Biol Chem 1986; 261: 1267-1273
34 Stump DC, Lijnen HR, Collen D. Purification and characterization of a novel low molecular weight form of single chain urokinase-type plasminogen activator. J Biol Chem 1986; 261: 17120-17126
35 Stump DC, Thienpont M, Collen D. Purification and characterization of a novel inhibitor of urokinase from human urine. Quantitation and preliminary characterization in plasma J Biol Chem 1986; 261: 12759-12761
36 Kudryk B, Rohoza A, Ahadi M, Chin J, Wiebe ME. A monoclonal antibody with ability to distinguish between NH₂-terminal fragments derived from fibrinogen and fibrin. Mol Immunol 1983; 20: 1191-1200
37 Kudryk B, Rohoza A, Ahadi M, Chin J, Wiebe ME. Specificity of a monoclonal antibody for the NH₂-terminal region of fibrin. Mol Immunol 1984; 21: 89-94
38 Kudryk BJ, Grossman ZD, McAfee JG, Rosebrough SF. Monoclonal antibodies as probes for fibrin(ogen) proteolysis. In: Chatal JF. (ed) Monoclonal Antibodies in Immunoscintigraphy. CRC Press, Boca Raton; FL: 1988: 365-398
39 Burtin P, Chavanel G, Andre-Bougaran J, Gentile A. The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study Int J Cancer 1987; 39: 170-178
40 Astedt B, Hagerstrand I, Lecander I. Cellular localization in placenta of placental type plasminogen activator inhibitors. Thromb Haemostas 1986; 56: 62
41 Sakai T, Noguchi M, Kisiel W. Assembly of functional prothrombinase on tumor cell surfaces. Circulation 1988; 78: II121
42 Gordon SG, Franks JJ, Lewis BJ. Comparison of procoagulant activities in extracts of normal and malignant human tissue. J Natl Cancer Inst 1979; 62: 773-776
43 Dover R, Goeting NL, Taylor I, Roath OS, Francis JL. Factor X-activating activity in patients with colorectal carcinoma. Br J Surg 1987; 74: 1122-1124
44 Nemerson Y. Tissure factor and hemostasis. Blood 1988; 71: 1-8
45 Pineo GF, Brian MC, Gallus AS, Hirsh OS, Francis J, Hatton MM C, Regoeczi I. Tumors, mucus production, and hypercoagulability. Ann N Y Acad Sci 1974; 230: 262-270
46 Pineo GF, Regoeczi E, Hatton MWC, Brain MC. The activation of coagulation by extracts of mucus: a possible pathway of intravascular coagulation accompanying adenocarcinomas. J Lab Clin Med 1973; 82: 255-266
47 Noguchi M, Sakai T, Kisiel W. Induction of tissue factor on human endothelial cells by human tumor cell conditioned medium. J Cell Biol 1988; 107: 582 a
48 Dasmahapatra KS, Cheung NK, Spillert C, Lazaro E. An assessment of monocyte procoagulant activity in patients with solid tumors. J Surg Res 1987; 43: 158-163
49 Markus G, Camiolo SM, Kohga S, Madeja JM, Mittelman A. Plasminogen activator secretion of human tumors in short-term organ culture, including a comparison of primary and metastatic colon tumors. Cancer Res 1983; 43: 5517-5525
50 Kohga S, Harvey SR, Weaver RM, Markus G. Localization of plasminogen activators in human colon cancer by immunoperoxidase staining. Cancer Res 1985; 45: 1787-1796
51 Burtin P, Fondaneche MC. Receptor for plasmin on human carcinoma cells. J Natl Cancer Inst 1988; 80: 762-765
52 Stadnicki A, Kacperek T, Nowak A, Gorka Z, Rudnicki M, Lempe P, Gonciarz Z. Modulatory effect of the gastrointestinal tract (gut) on fibrinolysis and fibrinogen derivatives. Scand J Gastroenterol 1987; 22: 539-542
53 Reich R, Thompson EW, Iwamoto Y, Martin GR, Deason JR, Fuller GC, Miskin R. Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells. Cancer Res 1988; 48: 3307-3312
54 Tissot JD, Hauert J, Bachmann F. Characterization of plasminogen activators from normal human breast and colon and from breast and colon carcinomas. Int J Cancer 1984; 34: 295-302
55 Cajot JF, Sordat B, Kruithof EK, Bachman F. Human primary colon carcinomas xenografted into nude mice. I. Characterization of plasminogen activators expressed by primary tumors and their xenografts. J Natl Cancer Inst 1986; 77: 703-712
56 Kirchheimer JC, Huber K, Wagner O, Binder BR. Pattern of fibrinolytic parameters in patients with gastrointestinal carcinomas. Br J Haematol 1987; 66: 85-89
57 Newstead GL, Griffiths JD, Salsbury AJ. Fibrinolytic activity of carcinoma of the colon. Surg Gyn Obstet 1976; 143: 61-64
58 Salsbury AJ, White C, Tsolakidis P, McKenna JA, Griffiths JD. Fibrinolysis and circulating malignant cells. Surg Gyn Obstet 1987; 136: 733-736
59 Irimura T, Yamori T, Bennett SC, Ota DM, Cleary KR. The relationship of collogenolytic activity to stage of human colorectal carcinoma. Int J Cancer 1987; 40: 24-31
60 Boyd D, Floren G, Kim P, Brattain M. Determination of the levels of urokinase and its receptor in human colon carcinoma cell lines. Cancer Res 1988; 48: 3112-3116
61 Appella E, Robinson EA, Ullrich SJ, Stoppelli MP, Corti A, Cassani G, Blasi F. The receptor binding sequence of urokinase. A biological function for the growth-factor module of proteases J Biol Chem 1987; 262: 4437-4440
62 Stoppelli MP, Tacchetti C, Cubellis MV, Corti A, Hearing VJ, Cassani G, Appella E, Blasi F. Autocrine saturation of pro-urokinase receptors on human A431 cells. Cell 1986; 45: 675-684
63 Rodeck U, Herlyn M, Herlyn D, Molthoff C, Atkinson B, Varello M, Steplewski Z, Koprowski H. Tumor growth modulation by a monoclonal antibody to the epidermal growth factor receptor: immunologically mediated and effector cell-independent effects. Cancer Res 1987; 47: 3692-3696
64 Calvo FA, Harguindey SS, Aparicio LA, Dy C, Gil A, Rocha E. Urokinase and combination chemotherapy for treatment of small cell carcinoma of the lung. Cancer Treat Sympos 1985; 2: 105-108