Dynamic analysis of cancer cells cytoskeleton during drug treatment

Abstract

Metastatic cancer, the leading cause of cancer-related death, it occurs when cancer cells leave the primary tumor and spread to distant organs such as bone, liver, and the lungs. Migrating cancer cells, 'riding the waves of interstitial fluid, preferentially migrate towards and intravasate into the circulatory and lymphatic systems, to aid their quest for seeking new tissue to seed secondary tumors. There have been numerous treatments to prevent the spread of cancer cells from the primary tumor; this includes chemotherapies, hormones, radiotherapy, and drug therapies. Most of these treatments have side effects that in most of the cases influence other tissues of the body leading to complication in patients health. Cancer cells invasion and intravasation depends on the migration of the cell which by itself is guided by the cytoskeletal movement. Some pharmaceutical companies have come up with drugs that target the cytoskeleton of the tumor cell in order to paralyze it and prevent it from leaving the primary tumor location. We investigated the influence of these drugs on the cytoskeleton of the MDA 231 breast cancer cells in order to determine the minimum dosage needed to either arrest or slowdown migration. Cancer cells compared to other cells do not have a well-defined cytoskeleton as result we had to use a novel quantification technique that can account for the complex structure of the cytoskeleton and the differences from one cell to another. We propose to use fractal analysis to measure the differences in cytoskeleton arrangement between cells exposed to different drugs. The novelty of this work is the ability to non-invasively screen the effects of various cytoskeletal drugs that specifically targets the cytoskeleton of cancer cells. Moreover, this method will allow us to quantify the cytoskeletal structure rearrangement in dynamic tumor cells. It was found that fractals combined with morphological descriptors can determine the minimum effective concentration of a certain drug, in addition to identify which toxins can be used to treat cancer and which cannot be used. In addition to that we were able to determine the minimum concentration(s) that can induce a change in the network organization of the cytoskeleton.

Date of Award	Dec 2015
Original language	American English
Supervisor	Jeremy Teo (Supervisor)