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Haidery, Ahmad Zia (2015) The role of microvesicles in EMT and tumour microenvironment. Doctoral thesis, London Metropolitan University.
Microvesicles are heterogeneous population of micro-particles released constitutively and upon induction from healthy and unhealthy cells. The role of cancer cell derived-MV in intercellular communication gains an intensive aria of research. The influence of leukaemia cell derived-MVs in this study was determined on normal prostate epithelial cell lines. PNT2 cells were treated with Jurkat cell derived-MVs lost epithelial characteristic (decreased epithelial marker E-cadherin) and gained mesenchymal phenotype (increased expression of mesenchymal marker Vimentin).
TGF-β and intracellular Ca2+ concentration were partially involved in Epithelial Mesenchymal Transition (EMT) process. PNT2 cells acquire mesenchymal characteristic produced high level of resistances against apoptotic signals after exposed to serum starvation and anti-cancer drug docetaxel, produce excessive level of MMP-9 and 2/3 of total TPNT2 cell population were arrested in the G2/M phase of the cell cycle, and halts cell proliferation.
The influence of carcinoma cell derived-MVs on tumour microenvironment was examined through use of Non-small lung cancer cells (A549) derived-MVs on primary lung fibroblasts (MRC5). MRC5 cells were treated with A549 cell derived-MV produced significantly high level of myofibroblasts marker alpha-smooth muscle actin (α-SMA) cytoskeleton protein and FGF. MVs were isolated from the myofibroblasts were enriched with α-SMA protein. Primary fibroblasts were treated with MVs released myofibroblasts expressed high level of α-MSA protein. Elements present in the CGM cause aggregation of cancer cell MVs and significantly reduced the effects of MVs on the target cells.
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