The role of integrins in various aspects of tumor biology including tumor growth, angiogenesis, invasion and metastasis is well established. However, the integrin-specific involvement in these processes in non-small cell lung cancer (NSCLC) cells has not been thoroughly investigated. This study focuses on the role of integrins in cell motility and anoikis in NSCLC with an in vitro model system using the lung adenocarcinoma cell line A549 and its paclitaxel resistant derivative A549-T24. This research includes the following three parts:
In order to demonstrate whether stimulation of the signaling mediated through specific integrins can differentially sensitize A549 and T24 cells to anchorage dependent apoptosis (anoikis), flow cytometry was used to detect the percentage of cells in certain apoptotic stages. T24 cells treated with an antibody to αvβ3 integrin showed more early apoptosis than A549 treated with the same anti-integrin antibody.
To determine the involvement of integrins in mediating the motility of A549 and T24 cells, μ-slide chemotaxis chambers was used to detect chemotactic responses of migrating cells with or without treatment with anti-αvβ3 integrin. When treated with the antibody, both T24 and A549 cells attach less and move slower compared to untreated cells. In addition, the anti-integrin antibody caused a greater reduction of velocity of cell movement in T24 cells compared with A549 cells.
To understand the survival signaling pathway activated by specific integrin extracellular matrix (ECM) interactions, a western blot analysis was performed to demonstrate that the PI3K pathway was involved in integrin-ECM interactions inactivating BAD for cell survival in T24 cells.
Overall, specific integrin modulation in T24 cells resistant to paclitaxel may acquire some of their more-aggressive characteristics including rescuing from anoikis and accelerating cell movement.
| Identifer | oai:union.ndltd.org:pacific.edu/oai:scholarlycommons.pacific.edu:uop_etds-4089 |
| Date | 01 January 2008 |
| Creators | Yang, Hong |
| Publisher | Scholarly Commons |
| Source Sets | University of the Pacific |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | University of the Pacific Theses and Dissertations |
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