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- W1559090524 abstract "Terminal prostate cancer is the result of metastatic spread of the tumourfrom the prostate and is the 2nd leading cause of cancer deaths in men.Although in vitro assays have been developed to screen for inhibitors ofprostate cancer metastasis and cell migration, they routinely utilise 2-Demensional (2-D) culture of prostate cancer cell lines. Current assays do notsimulate complexity of the in vivo human tumour microenvironment whichcontains a mixture of normal and transformed epithelial cells and stromalcells. Therefore there is a requirement to develop novel 3-D models torecapitulate the in vivo tumour microenvironment to understand tumourstroma function. Utilising a 3-D co-culture spheroid model incorporatingprimary human tumour stroma with prostate cancer cells we have shownthat the stroma has a key role in prostate cancer epithelial cell migration andmotility. By utilising 4-D two-photon imaging and gene expression analysiswe have analysed the molecular mechanisms of stromal cell mediatedprostate cancer cell migration, identifying genes that regulate the migrationprocess.Analysis of human tumour stroma indicates a key role in the immune systemin driving tumour stroma to express a lymphoid stromal phenotype thatprovides the microenvironment for active tumour cell migration. This offersan interesting dichotomy that the formation of lymphoid like stroma inaggressive tumours may paradoxically deliver help to drive the immuneresponse to the tumour whilst simultaneously providing themicroenvironment for tumour cell migration and metastasis.The molecular mechanism of prostate cancer cell migration and metastasisand stroma-epithelial cell interactions involves a complex balance betweenthe adhesion molecule VCAM-1 and two counter ligands VLA-4 and SPARC,also known as osteonectin or BM-40. The utilisation of shRNA knockdown,Fc chimeric proteins and blocking antibodies, indicates a key role forstromal-epithelia adhesion and detachment dependent cell migrationmediated by VCAM-1, VLA-4 and SPARC." @default.
- W1559090524 created "2016-06-24" @default.
- W1559090524 creator A5032095536 @default.
- W1559090524 date "2012-09-01" @default.
- W1559090524 modified "2023-09-24" @default.
- W1559090524 title "The Role of Stroma Microenvironments in Prostate Cancer Cell Migration and Metastasis" @default.
- W1559090524 hasPublicationYear "2012" @default.
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