Related Experiment Video
Updated: Jun 27, 2026
Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
Paclitaxel downregulates tissue factor in cancer and host tumour-associated cells
Emanuela Napoleone1, Filomena Zurlo, Maria Carmela Latella
1Laboratory of Thrombosis and Cancer Research, Research Laboratories, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Largo Gemelli, 1, 86100 Campobasso, CB, Italy.
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 degrees 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-1beta 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-alpha and IL-1beta 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-1beta release from the cells used in this paper. Neither the constitutive expression of IL-6 and IL-1beta 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.
Insights
Paclitaxel, an anti-cancer drug, reduces tissue factor (TF) activity and expression in cancer cells and associated cells. This modulation of TF
Area of Science:
- Oncology
- Molecular Biology
- Hematology
Background:
- Paclitaxel is a potent anti-tumour agent used in various cancers.
- Tissue factor (TF) is crucial in cancer progression and is expressed by tumor cells, endothelial, and inflammatory cells.
- Modulating TF presents a therapeutic strategy for cancer treatment.
Purpose of the Study:
- To investigate the effect of paclitaxel on tissue factor (TF) expression and activity in cancer and host cells.
- To determine if paclitaxel influences procoagulant activity, TF antigen, and mRNA levels.
- To assess paclitaxel's impact on inflammatory cytokine release.
Main Methods:
- Human mononuclear cells (MN), human umbilical vein endothelial cells (HUVEC), and MDA-MB-231 breast cancer cells were treated with paclitaxel.
- Procoagulant activity was measured using a one-stage clotting assay.
- TF antigen and mRNA levels were quantified by ELISA and real-time RT-PCR, respectively.
- Interleukin-6 (IL-6) and Interleukin-1beta (IL-1beta) levels were measured in conditioned media.
Main Results:
- Paclitaxel significantly reduced constitutive TF activity and antigen in MDA-MB-231 cells.
- Paclitaxel inhibited LPS-, TNF-alpha-, and IL-1beta-induced TF in MN cells and HUVEC.
- A decrease in TF mRNA levels was observed in the presence of paclitaxel.
- Paclitaxel did not affect constitutive or induced release of IL-6 and IL-1beta.
Conclusions:
- Paclitaxel effectively modulates the procoagulant potential of cancer and host cells by reducing TF expression and activity.
- The anti-tumour effects of paclitaxel may be partly attributed to its ability to inhibit TF.
- Paclitaxel's impact on TF, independent of inflammatory cytokine modulation, offers a novel therapeutic insight.
Related Concept Videos
01:15Drugs that Stabilize Microtubules
02:17The Tumor Microenvironment
01:31The Intrinsic Apoptotic Pathway
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:27Tumor Immunotherapy