Poster Presentation 30th Lorne Cancer Conference 2018

Proteomic analysis of the mouse brain stromal microenvironment: a milieu intérieur of metabolic reprogramming (#183)

Priyakshi Kalita-de Croft 1 2 , Jasmin Straube 2 , Fares Al-Ejeh 2 , Jodi M Saunus 1 2 , Sunil R Lakhani 1 3
  1. University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia
  2. QIMR Berghofer, Brisbane, QLD, Australia
  3. Pathology Queensland, Royal Brisbane Women's Hospital, Brisbane, Queensland, Australia

The tumour microenvironment (TME) is the site of intense interplay between neoplastic cells, immune cells and stromal cells, with the extracellular matrix and its associated signalling molecules providing both the framework and mechanism for much of this interaction. Successful expansion of tumours at secondary sites occur despite an immense negative selection pressure imposed upon invading cells by this environment. The brain microenvironment comprises of unique cell types and is particularly harsh, yet invading tumour cells become adept at survival and expansion through a range of adaptive mechanisms that include: oxidative stress survival, the repurposing of neurotransmitters as metabolic substrates and the mimicking of neural traits [1-7]. Such transformations could be clinically translatable/targetable and hence we set out to perform a proteomic analysis of the mouse brain stroma to identify novel adaptation pathways utilised by the tumour cells to colonise the brain. Breast cancer cell line MDA-MB 231 was injected into NOD/SCID mice (n=5) intracranially using a stereotaxic frame. PBS (n=4) was used for the mock injections and the left frontal posterior part of the brain from the same animals was used as an uninvolved control. After three weeks of tumour-engraftment, brain tissue surrounding the developing tumour was separated and analysed using Mass Spectrometry (MS)-Swath analysis at the Australian Proteome Analysis Facility (APAF), New South Wales. Bioinformatics analysis revealed that the tumour associated brain exhibited deregulation of pathways involving metabolic stress and extracellular vesicle transport such as mitochondrial dysfunction, oxidative phosphorylation, sirtuin signalling and cell death and survival pathways. These findings suggest that tumour associated brain undergoes metabolic reprogramming which could potentially aid in tumour establishment. Targets involved in this process are being currently assessed in clinical samples. 

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