Abstract
Paclitaxel, a microtubule-stabilising compound with potent anti-tumour activity, has
been clinically used in a wide variety of malignancies. Tissue factor (TF) is often
expressed by tumour-associated endothelial and inflammatory cells, as well as by cancer
cells themselves, and it is considered a hallmark of cancer progression.
We investigated whether paclitaxel could modulate TF in human mononuclear (MN) cells,
human umbilical vein endothelial cells (HUVEC) and the metastatic breast carcinoma
cell line MDA-MB-231.
Cells were incubated with or without paclitaxel at 37 °C. At the end of incubation, cells were disrupted and tested for procoagulant activity
by a one-stage clotting assay, for TF antigen levels by ELISA and TF mRNA by real-time
RT-PCR. IL-6 and IL-1β were tested by ELISA in conditioned medium.
Both the strong TF activity and antigen constitutively expressed by MDA-MB-231 and
the TF induced by LPS, TNF-α and IL-1β in MN cells and HUVEC were significantly reduced
by paclitaxel. In the presence of paclitaxel, lower TF mRNA levels were also detected.
Since paclitaxel has been shown to induce the expression of inflammatory genes in
monocytes and tumour cells, we tested whether paclitaxel could influence IL-6 and
IL-1β release from the cells used in this paper. Neither the constitutive expression
of IL-6 and IL-1β by MDA-MB-231 nor the basal and LPS-induced release from MN cells
and HUVEC was affected.
Our data support the hypothesis that the anti-tumour effects of paclitaxel may, at
least in part, be mediated by the capacity of this drug to modulate the procoagulant
potential of cancer and host cells.
Keywords
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References
- The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents.Annu Rev Med. 1997; 48: 353-374
- Microtubules and actin filaments: dynamic targets for cancer chemotherapy.Curr Opin Cell Biol. 1998; 10: 123-130
- Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages.J Leukoc Biol. 1992; 52: 119-121
- Effects of paclitaxel on cytokine synthesis by unprimed human monocytes, T lymphocytes, and breast cancer cells.Cancer Immunol Immunother. 1998; 46: 104-112
- Taxane-mediated gene induction is independent of microtubule stabilization: induction of transcription regulators and enzymes that modulate inflammation and apoptosis.Proc Natl Acad Sci USA. 1998; 95: 3896-3901
- Effect of taxol and taxotere on gene expression in macrophages: induction of the prostaglandin H synthase-2 isoenzyme.J Immunol. 1999; 162: 467-473
- Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines.Cytokine. 2001; 15: 156-165
- Paclitaxel at ultra low concentrations inhibits angiogenesis without affecting cellular microtubule assembly.Anticancer Drugs. 2003; 14: 13-19
- Tissue factor and hemostasis.Blood. 1988; 71: 1-8
- The role of blood clotting in tumor metastasis: a case for tissue factor.in: Lugassy G. Falanga A. Kakkar A.K. Rickles F.R. Thrombosis and cancer. Martin Dunitz Limited, London2004: 47-58
- Tissue factor, thrombin, and cancer.Chest. 2003; 124: 58S-68S
- Cancer cell procoagulants and their pharmacological modulation.Haemostasis. 1984; 14: 422-429
- Tissue factor and cancer metastasis: the role of intracellular and extracellular signaling pathways.Mol Med. 2004; 10: 6-11
- Thrombin generation and the pathogenesis of cancer.Semin Thromb Hemost. 2006; 32: 61-68
- Requirement for binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis.J Clin Invest. 1998; 101: 1372-1378
- Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation.Proc Natl Acad Sci USA. 1995; 92: 8205-8209
- Regulation of angiogenesis by tissue factor cytoplasmic domain signaling.Nat Med. 2004; 10: 502-509
- Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues.Blood. 1983; 62: 271-273
- Monocyte procoagulant activity as a peripheral marker of clotting activation in cancer patients.Haemostasis. 1988; 18: 55-65
- The biology and tumour-related properties of monocyte tissue factor.J Pathol. 2001; 193: 3-12
- In situ detection of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast disease.Nature Med. 1996; 2: 209-215
- The role of tunor- and host-related tissue factor pools in oncogene-driven tumor progression.Thromb Res. 2007; 120: S82-S91
- Monocytes upregulate endothelial cell expression of tissue factor: a role for cell–cell contact and cross-talk.Blood. 1997; 89: 541-549
- Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.Methods. 2001; 25: 402-548
- Pathogenesis of thrombosis in patients with malignancy.Int J Hematol. 2001; 73: 137-144
- From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer.J Thromb Haemost. 2003; 1: 1456-1463
- Cell–cell interaction and tissue factor expression.Blood Coagul Fibrinol. 1998; 9: S49-59
- The immunopharmacology of paclitaxel (Taxol), docetaxel (Taxotere), and related agents.Int Immunopharmacol. 2003; 3: 1699-1714
- The taxanes: an update.Lancet. 2000; 355: 1176-1178
- The microtubule-affecting drug paclitaxel has antiangiogenic activity.Clin Cancer Res. 1996; 2: 1843-1849
- Controlled releases of FGF-2 and paclitaxel from chitosan hydrogels and their subsequent effects on wound repair, angiogenesis, and tumor growth.Curr Drug Deliv. 2006; 3: 351-358
- Paclitaxel (Taxol): an inhibitor of angiogenesis in a highly vascularized transgenic breast cancer.Cancer Biother Radiopharm. 1999; 14: 31-36
- The range of optimal concentration and mechanisms of paclitaxel in radio-enhancement in gastrointestinal cancer cell lines.Cancer Chemother Pharmacol. 2007; 59: 733-742
- The efficacy of Paclitaxel on solid tumour analysed by ATP bioluminescence assay and VEGF expression: a translational research study.Biomed Pharmacother. 2005; 59: S337-S339
- Role of tissue factor in embryonic blood vessel development.Nature. 1996; 383: 73-75
- Contribution of the hemostatic system to angiogenesis in cancer.Semin Thromb Hemost. 2004; 30: 5-20
- Tissue factor and fibrin in tumor angiogenesis.Semin Thromb Hemost. 2004; 30: 31-44
- Taxol increases steady-state levels of lipopolysaccharide-inducible genes and protein-tyrosine phosphorylation in murine macrophages.J Immunol. 1992; 149: 2459-2465
- Structural significance of the acyl group at the C-10 position and the A ring of the taxane core of paclitaxel for inducing nitric oxide and tumor necrosis factor production by murine macrophages.FEBS Lett. 2000; 478: 221-226
- Paclitaxel enhances thrombin-induced endothelial tissue factor expression via c-Jun terminal NH2 kinase activation.Circ Res. 2006; 99: 149-155
- Vascular bed-specific thrombosis.J Thromb Haemost. 2007; 5: 283-291
- Tissue-specific hemostasis in mice.Arteriscler Thromb Vasc Biol. 2005; 25: 2273-2281
- Upregulation of tissue factor expression and thrombogenic activity in human aortic smooth muscle cells by irradiation, rapamycin and paclitaxel.Int Immunopharmacol. 2008; 8: 307-311
Article info
Publication history
Published online: December 01, 2008
Accepted:
October 17,
2008
Received:
October 14,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
