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Mechanical Properties of Cancer Cells: A Possible Biomarker for Stemness

Mohammadalipour, Ameneh

Abstract Details

2015, Doctor of Philosophy (PhD), Ohio University, Physics and Astronomy (Arts and Sciences).
In the past decade, defining the characteristics of cancer stem-like cells (CSCs) has become an important subject in cancer research. CSCs, which are a small fraction of cells in a tumor and have stem-like properties such as self-renewal and the ability to differentiate into multiple cancer cell types, are associated with the poor clinical outcomes in cancer treatment. Although molecular surface expression levels have been used for CSCs recognition, the clinical and prognostic impact of these markers have remained a controversial issue. Studies have shown that onset and progression of diseases such as malaria, sickle cell anemia and cancer have a direct relation to changes in the biomechanical properties of cells. The finding that cancerous cells are considerably more deformable than normal ones provides the motivation for the idea that the mechanical properties and deformability differences can be used as a biomarker to distinguish between stem-like and non-stem-like cancer cells. A number of biophysical techniques such as atomic force microscopy (AFM), and optical tweezers have been used to measure the mechanical properties of cancerous cells. In this study, we used the micropipette aspiration and particle-tracking microrheology techniques to investigate the biomechanical property differences between breast cancer cell lines with stem-like and non-stem-like phenotypes. Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer mortality in women after lung cancer. Using different models and procedures, we were able to measure the elasticity, viscosity and viscoelasticity of Hs578T and MDA-MB-231 breast cancer cell lines, which, based on the surface markers are stem-like, versus BT-20, MDA-MB-468, MCF-7, and ZR-75-1, which are known as non-stem-like breast cancer cell lines (non-BCSCs) according to the surface markers. We found that MDA-MB-468 cell line was the least deformable among the other cell lines having the largest elasticity, viscosity and viscoelasticity properties, while the Hs578T and MDA-MB-231 cell lines found to be the most deformable ones. BT-20 cell line had intermediate values for elasticity, viscosity, and viscoelasticity parameters. Also, it was found that the elasticity of the cancer cells was dependent on the rate of the pressure loading, suggesting a more complex rheology for the cancer cells. Using intracellular particle tracking, regional rheological differences were found for different regions of the cells. The overall result of this technique was in agreement with the results of micropipette aspiration. The enhanced deformability seen here for stem-like cancer cells can provide a mechanism for enhanced invasivity by allowing easier intravasation and extravasation during the metastatic process. Therefore, the differences in the rheological properties of cancer cells can be a potential biomarker for CSCs and can eventually enhance cancer diagnosis and therapy.
David Tees (Committee Chair)
Peter Jung (Committee Member)
Joseph Shields (Committee Member)
Monica Burdick (Committee Member)
Fabian Benencia (Committee Member)
117 p.

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Citations

  • Mohammadalipour, A. (2015). Mechanical Properties of Cancer Cells: A Possible Biomarker for Stemness [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420642948

    APA Style (7th edition)

  • Mohammadalipour, Ameneh. Mechanical Properties of Cancer Cells: A Possible Biomarker for Stemness. 2015. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420642948.

    MLA Style (8th edition)

  • Mohammadalipour, Ameneh. "Mechanical Properties of Cancer Cells: A Possible Biomarker for Stemness." Doctoral dissertation, Ohio University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1420642948

    Chicago Manual of Style (17th edition)