Tissue Factor and Cancer: Regulation, Tumor Growth, and Metastasis

Overview

Journal Semin Thromb Hemost

Publisher Thieme

Specialties Cardiology & Vascular Diseases
Hematology

Date 2019 May 17

PMID 31096306

Citations 72

Authors

Yohei Hisada

Nigel Mackman

Affiliations

Soon will be listed here.

Abstract

There is a strong relationship between tissue factor (TF) and cancer. Many cancer cells express high levels of both full-length TF and alternatively spliced (as) TF. TF expression in cancer is associated with poor prognosis. In this review, the authors summarize the regulation of TF expression in cancer cells and the roles of TF and asTF in tumor growth and metastasis. A variety of different signaling pathways, transcription factors and micro ribonucleic acids regulate TF gene expression in cancer cells. The TF/factor VIIa complex enhances tumor growth by activating protease-activated receptor 2 signaling and by increasing the expression of angiogenic factors, such as vascular endothelial growth factor. AsTF increases tumor growth by enhancing integrin β1 signaling. TF and asTF also contribute to metastasis via multiple thrombin-dependent and independent mechanisms that include protecting tumor cells from natural killer cells. Finally, a novel anticancer therapy is using tumor TF as a target to deliver cytotoxic drugs to the tumor. TF may be useful in diagnosis, prognosis, and treatment of cancer.

Citing Articles

Role of Coagulation Factors in Hepatocellular Carcinoma: A Literature Review.

Azam A, Klisic A, Mercantepe F, Faseeh H, Mercantepe T, Rafaqat S Life (Basel). 2025; 15(1).

PMID: 39859975 PMC: 11766868. DOI: 10.3390/life15010034.

Circulating, Extracellular Vesicle-Associated Tissue Factor in Cancer Patients with and without Venous Thromboembolism.

Lami V, Nieri D, Pagnini M, Gattini M, Donati C, De Santis M Biomolecules. 2025; 15(1.

PMID: 39858477 PMC: 11762650. DOI: 10.3390/biom15010083.

Immunoconjugates as an Efficient Platform for Drug Delivery: A Resurgence of Natural Products in Targeted Antitumor Therapy.

Mihaylova R, Momekova D, Elincheva V, Momekov G Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770542 PMC: 11677665. DOI: 10.3390/ph17121701.

Tissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies.

Takao S, Fukushima H, Furusawa A, Kato T, Okuyama S, Kano M Cancer Immunol Immunother. 2025; 74(2):48.

PMID: 39751657 PMC: 11699179. DOI: 10.1007/s00262-024-03903-2.

Preclinical evaluation of radiolabeled tissue factor-targeted peptide for theranostics of hepatocellular carcinoma post percutaneous ethanol injection.

Zhang B, Wang P, Chen Q, Yang Y, Xiong F, Bao G Theranostics. 2024; 14(19):7370-7382.

PMID: 39659572 PMC: 11626952. DOI: 10.7150/thno.102130.

References

Hu Z, Sun Y, Garen A . Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model. Proc Natl Acad Sci U S A. 1999; 96(14):8161-6. PMC: 22205. DOI: 10.1073/pnas.96.14.8161. View

Kakkar A, Chinswangwatanakul V, Lemoine N, Tebbutt S, Williamson R . Role of tissue factor expression on tumour cell invasion and growth of experimental pancreatic adenocarcinoma. Br J Surg. 1999; 86(7):890-4. DOI: 10.1046/j.1365-2168.1999.01153.x. View

Seto S, Onodera H, Kaido T, Yoshikawa A, Ishigami S, Arii S . Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis. Cancer. 2000; 88(2):295-301. DOI: 10.1002/(sici)1097-0142(20000115)88:2<295::aid-cncr8>3.0.co;2-u. View

Rak J, Mitsuhashi Y, Sheehan C, Tamir A, Viloria-Petit A, Filmus J . Oncogenes and tumor angiogenesis: differential modes of vascular endothelial growth factor up-regulation in ras-transformed epithelial cells and fibroblasts. Cancer Res. 2000; 60(2):490-8. View

Ueno T, Toi M, Koike M, Nakamura S, Tominaga T . Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration. Br J Cancer. 2000; 83(2):164-70. PMC: 2363475. DOI: 10.1054/bjoc.2000.1272. View

Hu Z, Garen A . Intratumoral injection of adenoviral vectors encoding tumor-targeted immunoconjugates for cancer immunotherapy. Proc Natl Acad Sci U S A. 2000; 97(16):9221-5. PMC: 16849. DOI: 10.1073/pnas.97.16.9221. View

Palumbo J, Kombrinck K, Drew A, Grimes T, Kiser J, Degen J . Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood. 2000; 96(10):3302-9. View

Hu Z, Garen A . Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer. Proc Natl Acad Sci U S A. 2001; 98(21):12180-5. PMC: 59788. DOI: 10.1073/pnas.201420298. View

Amirkhosravi A, Meyer T, Chang J, Amaya M, Siddiqui F, Desai H . Tissue factor pathway inhibitor reduces experimental lung metastasis of B16 melanoma. Thromb Haemost. 2002; 87(6):930-6. View

10.

Chambers A, Groom A, MacDonald I . Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002; 2(8):563-72. DOI: 10.1038/nrc865. View

11.

Liu C, Huang H, Donate F, Dickinson C, Santucci R, El-Sheikh A . Prostate-specific membrane antigen directed selective thrombotic infarction of tumors. Cancer Res. 2002; 62(19):5470-5. View

12.

Palumbo J, Potter J, Kaplan L, Talmage K, Jackson D, Degen J . Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res. 2002; 62(23):6966-72. View

13.

Bogdanov V, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y . Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med. 2003; 9(4):458-62. DOI: 10.1038/nm841. View

14.

Darmoul D, Gratio V, Devaud H, Lehy T, Laburthe M . Aberrant expression and activation of the thrombin receptor protease-activated receptor-1 induces cell proliferation and motility in human colon cancer cells. Am J Pathol. 2003; 162(5):1503-13. PMC: 1851194. DOI: 10.1016/S0002-9440(10)64283-6. View

15.

Francisco J, Cerveny C, Meyer D, Mixan B, Klussman K, Chace D . cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003; 102(4):1458-65. DOI: 10.1182/blood-2003-01-0039. View

16.

Hembrough T, Swartz G, Papathanassiu A, Vlasuk G, Rote W, Green S . Tissue factor/factor VIIa inhibitors block angiogenesis and tumor growth through a nonhemostatic mechanism. Cancer Res. 2003; 63(11):2997-3000. View

17.

Poon R, Lau C, Ho J, Yu W, Fan S, Wong J . Tissue factor expression correlates with tumor angiogenesis and invasiveness in human hepatocellular carcinoma. Clin Cancer Res. 2003; 9(14):5339-45. View

18.

Mueller B, Reisfeld R, Edgington T, Ruf W . Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci U S A. 1992; 89(24):11832-6. PMC: 50651. DOI: 10.1073/pnas.89.24.11832. View

19.

Akashi T, Furuya Y, Ohta S, Fuse H . Tissue factor expression and prognosis in patients with metastatic prostate cancer. Urology. 2003; 62(6):1078-82. DOI: 10.1016/s0090-4295(03)00768-4. View

20.

Camerer E, Qazi A, Duong D, Cornelissen I, Advincula R, Coughlin S . Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood. 2004; 104(2):397-401. DOI: 10.1182/blood-2004-02-0434. View