Brain Metastases · The Role of Circulating Monocytes in the Development of Brain Metastases
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-05-01 → 2018-02-10
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
The Role of Circulating Monocytes in the Development of Brain Metastases
Brain metastasis of breast cancer is a devastating condition and carries a very poor prognosis. Patients that are diagnosed with spread to the brain survive between 3 and 23 months from diagnosis. Our understanding of how brain metastases develop is limited and closing this gap in knowledge will allow for improved therapies to be developed. One of the main gaps in our knowledge is how cells in the microenvironment contribute to brain metastasis, particularly those of the innate immune system such as monocytes/macrophages. The goal of this fellowship was to determine how monocytes and macrophages originating from the blood participate in the development of brain metastases from breast cancer and identify potential therapeutic routes. To study the blood-derived population specifically, we have used a mouse strain where the monocytes and macrophages have been genetically engineered to express the protein eGFP, which fluoresces green, allowing us to trace the origin of the monocytes and macrophages in these mice. The objectives in this fellowship were as follows: (1) Characterize the recruitment of blood-derived monocytes and macrophages into brain metastases, and determine how this correlates disease progression. (2) Determine if inhibiting blood-derived monocyte and macropahge infiltration into the brain will reduce both the initiation and progression of metastases. (3) Determine if the blood-derived monocytes and macrophages are pro-inflammatory (tumour killing) or anti-inflammatory (tumour promoting) and if changing their characteristics will slow brain metastasis progression.
Data: CORDIS, © European Union
Project objective
Brain metastases, particularly from breast cancer, are a significant clinical problem. About one fifth of breastcancer patients that develop metastatic disease will experience brain metastases. Survival is extremely poor, with amedian survival of approximately three months. One of the main issues with treating brain metastases is the latestage at which the majority of brain metastases are diagnosed and the ineffectiveness of available therapies as aconsequence. At this late point, it is often too late for standard therapies to have a meaningful effect on theprogression of the tumours.In recent years, the role of the immune system in the progression of systemic metastases has been described, withcirculating monocytes being found to play a significant role. However, little is known about the pathogenesis ofmetastases within the brain. The brain possesses a very different environment to the rest of the body, with the bloodbrain barrier (BBB) tightly regulating the movement of nutrients, drugs and cells into the brain. Consequently, theprocesses that modeluate metastasis progression in other organs, such as lung and liver, may not be reflected withinthe brain owing to its unique environment. The overall goal of this fellowship, therefore, will be to determine therole of circulating monocytes in the development of brain metastases from breast cancer with the aim of identifyingpotential therapeutic routes.We believe that circulating monocytes may play a significant role in the development and progression of brainmetastases as a separate, distinct population from the resident macrophage population (microglia) within the brain.We hypothesize that there is significant circulating monocyte infiltration into brain metastases, which is associatedwith increased BBB breakdown and disease progression. On this basis, we propose that inhibiting these circulatingmonocytes will significantly reduce both initiation and progression of brain metastasis.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union