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Title: Influence of paracrine signalling within the tumour microenvironment on progression in breast cancer models
Author: Estévez Cebrero, María de los Ángeles
ISNI:       0000 0004 6423 3794
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2015
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Introduction: Cancer cells are affected by paracrine signalling from surrounding stromal cells. Here we investigate the role of kinases in this signalling using a model breast cancer (BC) co-culture system to identify novel paracrine signalling mechanisms supporting the growth and survival of tumour cells and potentially modulating epithelial to mesenchymal transition (EMT). Methods: The influence of paracrine signalling of the MSCs in the growth of luminal and basal-like breast cancer cells after the knock-down of human kinases, selected through a screen of a siRNA library, was investigated using a co-culture system that involves the culture of these transfected cells with or without human bone marrow-derived MSCs. An in silico analysis was also performed to investigate potential clinical relevance of these molecules. Results: The screen of the human kinase siRNA library in the MCF-7 cells co-cultured with MSCs revealed a number of kinases that seemed to be involved in the regulation of tumour growth. The knock-down of a subset, including GKAP1, CALM2, NEK7, MAPK7 and PI3KC2G, in the MCF-7, MDA-MB-231 and BT-549 cells growing alone or with MSCs resulted in the modulation of growth through autocrine or paracrine pathways and some may also be involved in the activation of the EMT pathways. Conclusion: There is a need for novel cancer biomarkers and targets to treat some forms of tumours such as the triple-negative BC, lacking a targeted therapy, or those that are resistant to the available ones. Here, the importance of the tumour microenvironment (TME) in the response to the inhibition of the targets in the cells was demonstrated. Potential therapeutic targets and pathways were presented as novel candidates for new treatments that need further investigation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available