ArticleJournal of experimental & clinical cancer research : CR2019
Impact of Docetaxel on blood-brain barrier function and formation of breast cancer brain metastases.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Demonstration of chemotherapeutic-mediated changes in meningeal lymphatics in vitro, ex vivo, and in vivo.Communications biology · 2025Article
- Prognostic Factors in Therapy Regimes of Breast Cancer Patients with Brain Metastases: A Retrospective Monocentric Analysis.Cancers · 2025Article
- Genetic and clinical correlates of two neuroanatomical AI dimensions in the Alzheimer's disease continuum.Translational psychiatry · 2024Article
- The Role of Microglia in Brain Metastases: Mechanisms and Strategies.Aging and disease · 2024Review
- Experimental models for cancer brain metastasis.Cancer pathogenesis and therapy · 2024Review
- Molecular signaling network and therapeutic developments in breast cancer brain metastasis.Advances in cancer biology - metastasis · 2023Article
- A flow cytometry-based protocol for syngenic isolation of neurovascular unit cells from mouse and human tissues.Nature protocols · 2023Review
- The Journey of Cancer Cells to the Brain: Challenges and Opportunities.International journal of molecular sciences · 2023Review
- Redox imbalance induced by docetaxel in the neuroblastoma SH-SY5Y cells: a study of docetaxel-induced neuronal damage.Redox report : communications in free radical research · 2021Article
- Pharmacological Neurorescue in a Paclitaxel-Induced Chemobrain Model.Frontiers in behavioral neuroscience · 2021Article
- Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines.Cancer research · 2020Review
Corrections and comments
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Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
backgroundBreast cancer (BC) is the most frequent malignant tumor in females and the 2nd most common cause of brain metastasis (BM), that are associated with a fatal prognosis. The increasing incidence from 10% up to 40% is due to more effective treatments of extracerebral sites with improved prognosis and increasing use of MRI in diagnostics. A frequently administered, potent chemotherapeutic group of drugs for BC treatment are taxanes usually used in the adjuvant and metastatic setting, which, however, have been suspected to be associated with a higher incidence of BM. The aim of our study was to experimentally analyze the impact of the taxane docetaxel (DTX) on brain metastasis formation, and to elucidate the underlying molecular mechanism.
methodsA monocentric patient cohort was analyzed to determine the association of taxane treatment and BM formation. To identify the specific impact of DTX, a murine brain metastatic model upon intracardial injection of breast cancer cells was conducted. To approach the functional mechanism, dynamic contrast-enhanced MRI and electron microscopy of mice as well as in-vitro transendothelial electrical resistance (TEER) and tracer permeability assays using brain endothelial cells (EC) were carried out. PCR-based, immunohistochemical and immunoblotting analyses with additional RNA sequencing of murine and human ECs were performed to explore the molecular mechanisms by DTX treatment.
resultsTaxane treatment was associated with an increased rate of BM formation in the patient cohort and the murine metastatic model. Functional studies did not show unequivocal alterations of blood-brain barrier properties upon DTX treatment in-vivo, but in-vitro assays revealed a temporary DTX-related barrier disruption. We found disturbance of tubulin structure and upregulation of tight junction marker claudin-5 in ECs. Furthermore, upregulation of several members of the tubulin family and downregulation of tetraspanin-2 in both, murine and human ECs, was induced.
conclusionIn summary, a higher incidence of BM was associated with prior taxane treatment in both a patient cohort and a murine mouse model. We could identify tubulin family members and tetraspanin-2 as potential contributors for the destabilization of the blood-brain barrier. Further analyses are needed to decipher the exact role of those alterations on tumor metastatic processes in the brain.
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