Dabrafenib and Trametinib prolong coagulation through the inhibition of tissue factor in BRAFv600e mutated melanoma cells in vitro

Background Neoplastic cells promote a hypercoagulable state by the expression of cell surface proteins, such as tissue factor. In BRAFv600 mutated melanoma patients upon BRAF inhibitors, a hypercoagulable state correlates with prognosis, while a down-regulation of the hemostatic parameters is observ...

Full description

Saved in:
Bibliographic Details
Published inCancer cell international Vol. 19; no. 1; p. 223
Main Authors Scatena, Cristian, Franceschi, Sara, Franzini, Maria, Sanguinetti, Chiara, Romiti, Nadia, Caponi, Laura, Mandalà, Mario, Mazzanti, Chiara Maria, Naccarato, Antonio Giuseppe
Format Journal Article
LanguageEnglish
Published London BioMed Central 28.08.2019
BMC
Subjects
Angiogenesis
Biotechnology
Cancer
Cell growth
Cell lines
Cell surface
Coagulation
Coagulation factors
Dabrafenib
Experiments
Gene expression
Inhibitors
Kinases
MEK inhibitors
Melanoma
Primary Research
Proteins
Raf/MEK/ERK pathway
Real time
Ribonucleic acid
RNA
Targeted cancer therapy
Tissue factor
Tissues
Trametinib
Italy
Online AccessGet full text

Cover

More Information
Summary:Background Neoplastic cells promote a hypercoagulable state by the expression of cell surface proteins, such as tissue factor. In BRAFv600 mutated melanoma patients upon BRAF inhibitors, a hypercoagulable state correlates with prognosis, while a down-regulation of the hemostatic parameters is observed in patients responders as compared to non responders. The present study was intended to better clarify the strict relationship between coagulation mediators and target therapy in melanoma. Methods The expression of tissue factor was investigated after the treatment with the BRAF inhibitor Dabrafenib and the MEK inhibitor Trametinib in the BRAFv600e mutated melanoma cell lines A-375 and SK-MEL-28, together with its ability to activate the coagulation cascade. Results Dabrafenib and Trametinib caused the down-regulation of TF in both cell lines A-375 and SK-MEL-28. For the cell line A-375 the effect was evident both at RNA and procoagulant activity; for the cell line SK-MEL-28 only at RNA level without any variation of the protein. Interestingly, when in contact with plasma deficient of factor VII, both cell lines were not able to activate the coagulation cascade. Conclusions The present study provides the first in vitro observation that tissue factor expressed in melanoma cells may contribute to the modulation of the coagulation state of patients in the treatment with BRAF inhibitors.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1475-2867
1475-2867
DOI:10.1186/s12935-019-0938-3