EFFECT OF INTEGRIN α5 ON CANCER CELL MOTILITY IN 2D AND 3D MATRICES

Cancer;migration;cell motility;Chemical & Biomolecular Engineering

Byun, Jung MinWirtz, Denis ;

Johns Hopkins University

关键词: Cancer;    migration;    cell motility;    Chemical & Biomolecular Engineering;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/39416/BYUN-THESIS-2015.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

The main cause of cancer related deaths is results from metastasis of cancer, or the spread of cancer to secondary sites. In order to metastasize, cancer cell migration is necessary. Numerous studies in cancer biology have examined mechanisms of cancer cell migration possible target molecules to prevent metastasis of cancer cells. During the early stages of metastasis, cancer cells penetrate through the basement membrane and invade into the extracellular matrix (ECM). During cell migration, integrins which are transmembrane receptors bind to extracellular matrix (ECM) molecules which mediate cell attachment and the formation of focal adhesions. Among many integrins, integrin α5β1 is often overexpressed in many cancer cells. We utilized 2D and 3D assays with an APRW model analysis to investigate the effect of downregulation of integrin α5 on cell motility using the metastatic breast cancer cell line, MDA-MB-231. We decreased integrin α5 expression using shRNA. Cells were plated on top of fibronectin, fibrinogen and collagen 2D substrates. Then, they were also embedded in a 3D collagen matrix and 3D collagen matrices with fibronectin. 2D and 3D cell movements were analyzed using an APRW model, saying cell movements are highly anisotropic. Furthermore, we performed focal adhesion staining on 2D cells to test correlation with cell migrationComparing 2D and 3D cell motility, we were able to observe integrin α5 had a remarkable effect on cell motility for 3D but showed less of an effect for 2D. We tested the correlation between 2D motility and focal adhesion and concluded that focal adhesion is not a predictor for 2D migration. With an increasing amount of fibronectin in 3D collagen matrices, the cell migration has decreased possibly due to the gel structure alteration. By investigating different parameters for cell motilities, such as diffusivity and persistence time, we were able to test effect of downregulation of integrin α5 on cell motility in 3D. Finally, the APRW model provided better characterization of cell movement than measuring cell velocities from cell trajectories data. Downregulation of integrin α5 does not alter cell speed but decreases diffusivity and persistence of metastatic cancer cells.