期刊
MEMBRANES
卷 11, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/membranes11110880
关键词
metastatic breast cancer; extracellular vesicles; treatment response; quantitative proteomics
类别
资金
- Ada Bartholomew Trust
- Zonta Club of Peel
- Lions Medical Research Foundation
- National Health and Medical Research Council
- Medical Research Future Fund (MRFF)
- Fondo Nacional de Desarrollo Cientifico y Tecnologico [FONDECYT 1170809]
- Australian Government Research Training Program
- Richard Walter Gibbon Medical Research Fund
- Cancer Council of Western Australia
- Defeat DIPG ChadTough New Investigator Fellowship
- NHMRC [GNT1173892]
- College of Health, Medicine and Wellbeing from the University of Newcastle
This study aimed to quantitatively profile the proteomes of EVs isolated from blood samples of metastatic breast cancer patients to identify proteins associated with treatment response.
Breast cancer is the leading cause of cancer death in women. The majority of these deaths are due to disease metastasis, in which cancer cells disseminate to multiple organs and disrupt vital physiological functions. It is widely accepted that breast cancer cells secrete extracellular vesicles (EVs), which contain dynamic molecular cargo that act as versatile mediators of intercellular communication. Therefore, Evs. secreted by breast cancer cells could be involved in the development of metastatic disease and resistance to treatment. Moreover, changes in EV cargo could reflect the effects of therapy on their parent tumor cells. The aim of this feasibility study was to quantitatively profile the proteomes of Evs. isolated from blood samples taken from treatment sensitive and resistant metastatic breast cancer patients to identify proteins associated with responses. Three serial blood samples were collected from three patients with metastatic breast cancer receiving systemic therapy including a responder, a non-responder, and a mixed-responder. Evs. were isolated from plasma using size exclusion chromatography and their protein cargo was prepared for tandem mass tag (TMT)-labelling and quantitative analyses using two-dimensional high-performance liquid chromatography followed by tandem mass spectrometry. After filtering, we quantitatively identified 286 proteins with high confidence using a q value of 0.05. Of these, 149 were classified as EV associated candidate proteins and 137 as classical, high abundant plasma proteins. After comparing EV protein abundance between the responder and non-responder, we identified 35 proteins with unique de-regulated abundance patterns that was conserved at multiple time points. We propose that this proof-of-concept approach can be used to identify proteins which have potential as predictors of metastatic breast cancer response to treatment.
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