3DNSBT · Three-dimensional nanofiber scaffolds as a model for the study of brain tumour migration
FP7 — People (Marie Curie Actions)
- Duration
- 2012-07-01 → 2016-06-30
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
Three-dimensional nanofiber scaffolds as a model for the study of brain tumour migration
3DNSBT- Final report. Sean Lawler 3DNSBT only completed year 1, as the applicant moved outside the EU. The aim of the study was to use a novel cell migration assay based on electrospun biocompatible nanofibers made of polycaprolactone to understand further mechanisms of cell migration in glioblastoma. Significant Results Significant results are as follows: 1. Assessment of cell migration in nanofiber assays. Poster is attached to the year 1 report. A paper is currently in preparation for submission to a peer-reviewed journal in which nanofiber migration assays were used to characterize migratory behavior in a panel of paediatric glioblastoma cell lines. 2. We have obtained full ethical approval to begin a brain tumour bank at Leeds. Patient consent, anonymisation, and sample transit and storage were all features of the plan. 3. We have obtained microarray data (gene expression and microRNA) from glioblastoma cells migrating in the presence and absence of indirubin or lithium as anti-migratory treatments. There was not time available during the funding period to analyze this data fully, however, it has many interesting candidates that will be examined in the future. All EU funded future work will be acknowledged. 4. Optimization of transfection and assay conditions in preparation for a robotic high throughput screen on nanofibers.
Data: CORDIS, © European Union
Project objective
Brain tumours represent a formidable therapeutic challenge. A major obstacle to effective treatment is the fact that many tumours readily invade normal brain preventing complete surgical resection leading to inevitable tumour recurrence. It is difficult to predict invasive potential of individual tumours, there are no drugs currently available that specifically target invading tumour cells, and there is a lack of efficacious models of tumour invasion. In collaboration with colleagues in the USA I have been involved in the development of a novel in vitro migration assay based on the use of 3D nanofiber scaffolds that stimulate brain tumour cell migration, which we recently used for gene expression profiling to identify novel signaling pathways involved in invasion of the most agressive brain tumour, glioblastoma multiforme.Here, we will further develop this model in three ways. First, we will address the mechanisms involved in glioblastoma migration by profiling microRNA alterations in nanofiber migration assays. After validation of altered microRNAs, their effects on cell migration will be determined in the nanofiber assay, and relevant targets will be identified. The long-term goal of this aim is to identify novel anti-invasive therapeutic approaches. Second, we will investigate the potential of 3D nanofiber scaffolds as diagnostic tools, that may be used to predict the invasive potential of various patient brain tumours. This will be done using patient samples obtained from brain tumour surgeries at Leeds General Infirmary. Invasive potential of tumour biopsies will be determined in the nanofiber assay, and compared with patient progress over time. If there are indications of efficacy, funding will be sought elsewhere to carry out broader trials on large numbers of patients. Such a tool may prove invaluable for clinical decision making. Finally, we will determine the potential of the assay for future high throughput screens.
Original text from CORDIS.
Participants
- UNIVERSITY OF LEEDS · LeedsCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union