Defense Date

2015

Document Type

Thesis

Degree Name

Master of Science

Department

Biomedical Engineering

First Advisor

Rebecca L. Heise

Second Advisor

Christopher Lemmon

Third Advisor

Charles Chalfant

Abstract

The objective of this study is to investigate the role of microtubule based organelle, the primary cilia in lung adenocarcinoma by i) Quantifying the presence of primary cilia in several Non Small Cell Lung Cancer (NSCLC) cell lines in response to mechanical stimuli, ii) Attempting to determine the role of primary cilia in cell migration, iii) Investigating the effects of Paclitaxel(Taxol) resistance in lung cancer cells, iv) Analyzing the response of lung cancer cells to Smoothened Inhibitors and v) Determining the effects of Transforming Growth Factor Beta-1(TGF-β1) induced Epithelial to Mesenchymal Transition(EMT) in lung cancer cells. To ascertain the effects of primary cilia in the hall marks of tumor progression, several experiments involved prohibition of primary cilia formation by silencing IFT88, the gene responsible using small interfering RNA. Three out of the five cell lines tested, showed increased expression of primary cilia under mechanical stretch. IFT88 inhibition of H460 cells decreased their migration rate to the injury site under stretch conditions. Smoothened (SMO) Inhibitors decreased proliferation and migration rates in human lung adenocarcinoma cell lines (A549luc) similar to the effects observed in IFT88 silenced cells. IFT88 silenced A549luc cells showed a partial reversal of TGF-beta1 induced up-regulation of a mesenchymal marker. These results indicate that primary cilia play a role in the progression and metastasis of lung cancer by aiding the adhesion, proliferation, migration and EMT of lung cancer cells.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-7-2015

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