The role of microvesicles in EMT and tumour microenvironment

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.

HaideryAhmad_RoleOfMicrovesiclesInEMTAndTumourMicroenvironment.pdf - Accepted Version

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