Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(3-4):472–477. doi: 10.1038/sj.bjc.6690073

Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis

M Sawada 1,2, S Miyake 1,2, S Ohdama 1,2, O Matsubara 3, S Masuda 4, K Yakumaru 5, Y Yoshizawa 1,2
PMCID: PMC2362438  PMID: 10027315

Abstract

Tissue factor (TF) is an initiator of the extrinsic cascade of blood coagulation. Although recent studies have revealed a relationship between metastatic properties and TF expression in some neoplastic cells, the significance of TF in lung cancer, especially in non-small-cell lung cancer (NSCLC), is still unclear. In this study, TF was detected in NSCLC cell lines by functional study, Western blot analysis and immunocytochemical staining. TF levels in eight NSCLC cell lines were also quantitated by enzyme-linked immunosorbent assay (ELISA), and TF expression was evaluated in 55 specimens of surgically resected NSCLCs. NSCLC cell lines derived from metastatic lesions produced high levels of TF (48.3 ± 23.5 ng 10−6 cells, mean ± s.e.m.), whereas those derived from primary lesions produced low levels of TF (0.2 ± 0.1 ng 10−6 cells). Immunohistochemical studies disclosed significantly stronger staining for TF in cells from NSCLC patients with metastasis than in those without metastasis. Among the 28 patients with metastasis, ten were strongly positive, 16 were moderately positive and two were negative for TF. In contrast, among the 27 patients without metastasis, only two were strongly positive, 18 were moderately positive and seven were negative for TF. Therefore, malignant cells from patients with lung cancer produce various levels of TF, and TF may play an important role in the metastatic process. © 1999 Cancer Research Campaign

Keywords: tissue factor, lung cancer, non-small-cell lung cancer, metastasis

Full Text

The Full Text of this article is available as a PDF (597.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson A. S., Francis J. L., Witherow R. O., Snell M. E. Procoagulant properties of benign and malignant prostatic tissue. Br J Urol. 1994 Aug;74(2):204–209. doi: 10.1111/j.1464-410x.1994.tb16587.x. [DOI] [PubMed] [Google Scholar]
  2. Adamson A. S., Luckert P., Pollard M., Snell M. E., Amirkhosravi M., Francis J. L. Procoagulant activity may be a marker of the malignant phenotype in experimental prostate cancer. Br J Cancer. 1994 Feb;69(2):286–290. doi: 10.1038/bjc.1994.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bromberg M. E., Konigsberg W. H., Madison J. F., Pawashe A., Garen A. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8205–8209. doi: 10.1073/pnas.92.18.8205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Callander N. S., Varki N., Rao L. V. Immunohistochemical identification of tissue factor in solid tumors. Cancer. 1992 Sep 1;70(5):1194–1201. doi: 10.1002/1097-0142(19920901)70:5<1194::aid-cncr2820700528>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  5. Contrino J., Hair G. A., Schmeizl M. A., Rickles F. R., Kreutzer D. L. In situ characterization of antigenic and functional tissue factor expression in human tumors utilizing monoclonal antibodies and recombinant factor VIIa as probes. Am J Pathol. 1994 Dec;145(6):1315–1322. [PMC free article] [PubMed] [Google Scholar]
  6. Contrino J., Hair G., Kreutzer D. L., Rickles F. R. In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease. Nat Med. 1996 Feb;2(2):209–215. doi: 10.1038/nm0296-209. [DOI] [PubMed] [Google Scholar]
  7. Drake T. A., Morrissey J. H., Edgington T. S. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989 May;134(5):1087–1097. [PMC free article] [PubMed] [Google Scholar]
  8. Esumi N., Fan D., Fidler I. J. Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. Cancer Res. 1991 Sep 1;51(17):4549–4556. [PubMed] [Google Scholar]
  9. Gordon S. G., Franks J. J., Lewis B. Cancer procoagulant A: a factor X activating procoagulant from malignant tissue. Thromb Res. 1975 Feb;6(2):127–137. doi: 10.1016/0049-3848(75)90018-3. [DOI] [PubMed] [Google Scholar]
  10. Gunji Y., Gorelik E. Role of fibrin coagulation in protection of murine tumor cells from destruction by cytotoxic cells. Cancer Res. 1988 Sep 15;48(18):5216–5221. [PubMed] [Google Scholar]
  11. Itoh H., Kataoka H., Koita H., Nabeshima K., Inoue T., Kangawa K., Koono M. Establishment of a new human cancer cell line secreting protease nexin-II/amyloid beta protein precursor derived from squamous-cell carcinoma of lung. Int J Cancer. 1991 Sep 30;49(3):436–443. doi: 10.1002/ijc.2910490322. [DOI] [PubMed] [Google Scholar]
  12. Koyama T., Nishida K., Ohdama S., Sawada M., Murakami N., Hirosawa S., Kuriyama R., Matsuzawa K., Hasegawa R., Aoki N. Determination of plasma tissue factor antigen and its clinical significance. Br J Haematol. 1994 Jun;87(2):343–347. doi: 10.1111/j.1365-2141.1994.tb04919.x. [DOI] [PubMed] [Google Scholar]
  13. Mackman N. Regulation of the tissue factor gene. FASEB J. 1995 Jul;9(10):883–889. doi: 10.1096/fasebj.9.10.7615158. [DOI] [PubMed] [Google Scholar]
  14. Morrissey J. H., Fair D. S., Edgington T. S. Monoclonal antibody analysis of purified and cell-associated tissue factor. Thromb Res. 1988 Nov 1;52(3):247–261. doi: 10.1016/0049-3848(88)90084-9. [DOI] [PubMed] [Google Scholar]
  15. Ornstein D. L., Zacharski L. R., Memoli V. A., Kisiel W., Kudryk B. J., Hunt J., Rousseau S. M., Stump D. C. Coexisting macrophage-associated fibrin formation and tumor cell urokinase in squamous cell and adenocarcinoma of the lung tissues. Cancer. 1991 Sep 1;68(5):1061–1067. doi: 10.1002/1097-0142(19910901)68:5<1061::aid-cncr2820680525>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  16. Ruf W., Rehemtulla A., Edgington T. S. Antibody mapping of tissue factor implicates two different exon-encoded regions in function. Biochem J. 1991 Sep 15;278(Pt 3):729–733. doi: 10.1042/bj2780729. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith B. T. Cell line A549: a model system for the study of alveolar type II cell function. Am Rev Respir Dis. 1977 Feb;115(2):285–293. doi: 10.1164/arrd.1977.115.2.285. [DOI] [PubMed] [Google Scholar]
  18. Wilcox J. N., Smith K. M., Schwartz S. M., Gordon D. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2839–2843. doi: 10.1073/pnas.86.8.2839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zhang Y., Deng Y., Luther T., Müller M., Ziegler R., Waldherr R., Stern D. M., Nawroth P. P. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest. 1994 Sep;94(3):1320–1327. doi: 10.1172/JCI117451. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES