Exploring Possible Roles Of Organic Anion-Transporting Polypeptides In Invadopodia Function
- ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
- George Tabor (Creator)
- Institution
- Appalachian State University (ASU )
- Web Site: https://library.appstate.edu/
- Advisor
- Jennifer Cecile
Abstract: Drug resistant, invasive tumors are among the most devastating cancers. It is the goal of this project to explore the potential relationships between these two phenotypes in a variety of tissue culture model systems. Invadopodia are actin-rich protrusions of the cellular membrane involved in extracellular matrix remodeling that allow cancer cells to invade other tissues during metastasis. Organic anion transporting-polypeptides (OATPs) mediate xenobiotic exchange across the cellular membrane and are believed to colocalize with lipid raft domains (LRDs) and caveolin-1 in humans, two factors that are also required for invadopodia function in breast cancer and melanoma cells. These transporters are thought to contribute to the multi-drug resistance phenotype of stubborn tumors and are upregulated in multiple cancer cell lines. To determine if functional OATPs are present in invadopodia-competent cells, fluorescence transport assays were performed on human prostate (PC3, LNCaP) and breast (MDA-MB-231) cancer cells as well as a murine fibroblast (NIH-3T3) cell line overexpressing constitutively active Src (Src-3T3). All cell lines exhibited robust uptake of rhodamine-123 (Rh-123), a fluorescent substrate of OATP1A2. Furthermore, the uptake of Rh-123 by MDA-MB-231 and PC3 cells was likely protein-mediated as the fluorescence signals were reduced by 67% and 68% respectively when the transport assays were performed on ice. In addition, an inhibition assay indicated that OATP1A2 might be responsible for the observed uptake of Rh-123 by LNCaP cells grown in androgen-depleted conditions. These inhibition studies are ongoing, and future experiments will explore the ultimate downstream effects of OATP substrates on invadopodia morphology and function. If OATPs play a role in invadopodia activity, they may contribute to the enhanced invasive phenotype of certain cancers and therefore serve as viable therapeutic targets.
Exploring Possible Roles Of Organic Anion-Transporting Polypeptides In Invadopodia Function
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Created on 9/26/2016
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Additional Information
- Publication
- Thesis
- Tabor, G (2015) "Exploring Possible Roles Of Organic Anion-Transporting Polypeptides In Invadopodia Function" Unpublished Honor's Thesis. Appalachian State University, Boone, NC
- Language: English
- Date: 2016