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The role of integrins in melanoma progression and metastasisMarshall, John Francis January 1995 (has links)
No description available.
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Mathematical modelling of cancer cell invasion of tissue : discrete and continuum approaches to studying the central role of adhesionAndasari, Vivi January 2011 (has links)
Adhesion, which includes cell-to-cell and cell-to-extracellular-matrix adhesion, plays an important role in cancer invasion and metastasis. After undergoing morphological changes malignant and invasive tumour cells, i.e., cancer cells, break away from the primary tumour by loss of cell-cell adhesion, degrade their basement membrane and migrate through the extracellular matrix by enhancement of cell-matrix adhesion. These processes require interactions and signalling cross-talks between proteins and cellular components facilitating the cell adhesion. Although such processes are very complex, the necessity to fully understand the mechanism of cell adhesion is crucial for cancer studies, which may contribute to improving cancer treatment strategies. We consider mathematical models in an attempt to understand better the roles of cell adhesion involved in cancer invasion. Using mathematical models and computational simulations, the underlying complex biological processes can be better understood and their properties can be predicted that might not be evident in laboratory experiments. Cancer cell migration and invasion of the extracellular matrix involving adhesive interactions between cells mediated by cadherins and between cell and matrix mediated by integrins, are modelled by employing two types of mathematical models: a continuum approach and an individual-based approach. In the continuum approach, we use Partial Differential Equations in which cell adhesion is treated as non-local and formulated by integral terms. In the individual-based approach, we first develop pathways for cell-cell and cell-matrix adhesion using Ordinary Differential Equations and later incorporate the pathways in a simulation environment for multiscale computational modelling. The computational simulation results from the two different mathematical models show that we can predict invasive behaviour of cancer cells from cell adhesion properties. Invasion occurs if we reduce cell-cell adhesion and increase cell-matrix adhesion and vice versa. Changing the cell adhesion properties can affect the spatio-temporal behaviour of cancer cell invasion. These results may lead to broadening our understanding of cancer cell invasion and in the long term, contributing to methods of patient treatment.
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Investigation Of The Inflammatory Pathways In Spontaneously Differentiating Caco-2 CellsAstarci, Erhan 01 July 2011 (has links) (PDF)
Intestinal epithelial differentiation entails the formation of highly specialized cells with specific absorptive, secretory, digestive and immune functions. Cell-cell and cell-microenvironment interactions appear to be crucial in determining the outcome of the differentiation process. Using the Caco-2 cell line that can undergo spontaneous differentiation when grown past confluency, we observed a loss of VCAM1 (vascular cell adhesion molecule-1) expression while ICAM1 (intercellular cell adhesion molecule-1) expression was seen to be stable in the course of differentiation. Protein kinase C theta (PKC&theta / ) acted downstream of PKC to inactivate Inhibitor of kappa B (IB) and activate NF-&kappa / B in the undifferentiated cells and this axis was inhibited in the differentiated cells. The increase in ICAM1 expression in the differentiated cells was due to a transcriptional upregulation by C/EBP. The protein expressions of both ICAM-1 and VCAM-1, however, were found to decrease in the course of differentiation, with both proteins getting post-translationally degraded in the lysosome. Functionally, a decrease in adhesion to HUVEC
cells was observed in the differentiated Caco-2 cells. Thus, the regulation of ICAM-1 and VCAM-1, although both NF-B target genes, appear to be different in the course of epithelial differentiation.
microRNAs are known to regulate many cellular pathways. miR-146a, which is known to target NF-&kappa / B, was shown to be highly upregulated in differentiated Caco-2 cells. As a predicted target of miR-146a, mRNA and protein expression of MMP16 was inversely correlated with miR-146a during differentiation of Caco-2 cells. miR-146a could bind to the 3&rsquo / UTR of MMP16 and ectopic expression of miR-146a resulted in a decreased mRNA and protein expression of MMP16 in the undifferentiated Caco-2 and HT-29 cells. Functionally, decreased gelatinase activity determined by gelatin zymography and reduced invasion and migration through Transwells was observed.
In the final part of the thesis, the inhibition of NF-&kappa / B via PPAR&gamma / in 15-Lipoxygenase-1 (15LOX1) expressing cells was investigated. The expression of 15LOX1, a member of the inflammatory arachidonate cascade, could lower phosphorylation of I&kappa / B&alpha / and NF-&kappa / B DNA binding activity which was reversed with a 15LOX1 inhibitor. This inhibition was mediated by phospho-PPAR&gamma / , which in turn was phosphorylated by ERK1/2.
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