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THE EFFECT OF EXTRACELLULAR MATRIX COMPONENTS ON MOTILITY AND CHEMOSENSITIVITY OF SELECT OVARIAN CANCER CELL LINES

Flate, Elizabeth L.
http://rave.ohiolink.edu/etdc/view?acc_num=kent1353954902

Abstract Details

2012, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.
Ovarian cancer is the fifth leading cause of cancer-related death among women and is the deadliest of gynecologic cancers. During metastasis, cancer cells preferentially adhere to the peritoneal submesothelial extracellular matrix (ECM). In an effort to better understand the process of metastasis, the effect of ECM on migration and cisplatin (CDDP) resistance was tested in two ovarian cancer cell lines: OV2008 and C13. Both transwell migration and in vitro wound healing assays were used to show that OV2008 cells have a greater capacity for movement compared to the C13 cell line on uncoated surfaces. Total wound healing and directionality of individually migrating cells was assessed for all experiments. Results showed that collagen type I (COLL) increases the migratory ability of OV2008 and C13 cells by increasing the directional migration of cells. In contrast, it appears that fibronectin (FN) decreases the migratory ability of OV2008 cells by reducing their ability to directionally migrate. In order to determine if differences in gene expression were correlated with the different cell movement phenotypes observed when the cells were cultured on glass, COLL or FN, GeneChip microarrays were performed for each of the cells lines on all three surfaces. Of the genes that displayed differences between migratory phenotypes, PAK2 was chosen for further investigation. When both cell lines are cultured on COLL and treated with increasing concentrations of the PAK inhibitor (IPA-3), there is a dose-dependent response such that there is a decrease in migration with an increase in inhibitor concentration. Further experiments utilizing PAK2 knockdown via siRNA transfection demonstrated significantly reduced migration of OV2008 cells on COLL as compared to those receiving Control siRNA. FN appears to increase the sensitivity of C13 cells to 24 hours of 30 μM CDDP treatment. Further, PAK2 knockdown in OV2008 cells decreased survival following CDDP treatment. In conclusion, our results indicate that FN and COLL affect the motility of the selected ovarian cancer cells lines and this effect is likely mediated, at least in part, by PAK2. As PAK2 is involved in both motility and chemosensitivity, it should be further explored as a pro-metastatic gene in ovarian cancer.
John R.D. Stalvey, PhD (Committee Chair)
Brent Bruot, PhD (Committee Member)
Srinivasan Vijayaraghavan, PhD (Committee Member)
Soumitra Basu, PhD (Committee Member)
Roger Gregory, PhD (Committee Member)
124 p.
Biomedical Research
Ovarian Cancer; Metastasis; Extracellular Matrix

Recommended Citations

Citations

  • Flate, E. L. (2012). THE EFFECT OF EXTRACELLULAR MATRIX COMPONENTS ON MOTILITY AND CHEMOSENSITIVITY OF SELECT OVARIAN CANCER CELL LINES [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1353954902

    APA Style (7th edition)

  • Flate, Elizabeth. THE EFFECT OF EXTRACELLULAR MATRIX COMPONENTS ON MOTILITY AND CHEMOSENSITIVITY OF SELECT OVARIAN CANCER CELL LINES. 2012. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1353954902.

    MLA Style (8th edition)

  • Flate, Elizabeth. "THE EFFECT OF EXTRACELLULAR MATRIX COMPONENTS ON MOTILITY AND CHEMOSENSITIVITY OF SELECT OVARIAN CANCER CELL LINES." Doctoral dissertation, Kent State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=kent1353954902

    Chicago Manual of Style (17th edition)

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© 2012, all rights reserved.
This open access ETD is published by Kent State University and OhioLINK.