Investigating Mechanical Strain-Induced Phenotypic Changes on Prostate Cancer Cell Toward Metastasis Using a Three-Dimensional <i>In-Vitro</i> Model

As tumors enlarge and progress, tumor cells are exposed to a myriad of altered mechanical forces that could dramatically modify their behavior. The objective of this thesis is to utilize a three-dimensional (3D) <i>in-vitro</i> model to investigate mechanical strain-induced phenotypic changes in prostate cancer (PC3) cells, progressing cells toward metastasis. A novel mechanical loading platform, the UNIcycler, was developed to apply 1% uniaxial stretch to 3D collagen encapsulated PC3 constructs. In this study, strain was applied for 30 minutes daily for 3 days. The experimental groups included a control (unloaded) group, a cyclic loaded group (1Hz frequency), and a static loaded group (continuous strain application). The effect of mechanical strain on actin cytoskeletal organization was first investigated using a time lapse study. Following this, a larger data set was collected for further analyze cell elongation and actin polymerization. Finally, the effect of mechanical strain on cell invasive potential was investigated using a custom cell migration assay. Results showed static loading significantly increases cell elongation, as compared to control and cyclic loading conditions (p<0.001). Increased cell elongation is indicative of the morphological changes associated with epithelial-mesenchymal transition. Additionally, actin polymerization analysis shows static loading to significantly increase actin polymerization, compared to control and cyclic loading (p<0.001). This suggests possible increased migratory potential, as coordinated actin polymerization is crucial to cell migration. This, in conjugation with the increased migratory tendencies seen in static loaded samples, suggests static uniaxial stretch induces phenotypic changes which progress prostate cancer (PC3) cells toward metastasis. When combined, this body of works indicates the capability of the UNIcycler to model cancer cell metastasis in the 3D environment.

Name thesis:degree_name

Master of Science in Bioengineering

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Bioengineering

Grantor dc:publisher

University of Toledo

Year dc:date

2013

Author dc:creator

• Ditto, Maggie J.

Contributors dc:contributor

• Yildirim-Ayan, Eda

• Biomedical Engineering
• Prostate Cancer
• Mechanotransduction
• Three-Dimensional
• Cyclic

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=toledo1365162394

OAI identifier oai:identifier

oai:etd.ohiolink.edu:toledo1365162394