Kooser, Julia
(2021)
Tetraspanin dependent tunneling nanotubule formation mediates stromal and cancer cell interactions, and facilitates ovarian cancer metastasis.
Undergraduate Thesis, University of Pittsburgh.
(Unpublished)
This is the latest version of this item.
Abstract
Ovarian cancer is the most fatal gynecological cancer in the United States, due to the propensity for early metastasis. Tumor cells do not grow in isolation but reside within a complex environment termed the tumor microenvironment. Mesenchymal stem cells, which are multipotent stromal progenitor cells found within most tissues of the body, can support a pro-tumorigenic environment, especially when they are epigenetically reprogrammed to assume a cancer associated phenotype referred to as cancer-associated mesenchymal stem cells.
Our lab has shown that cancer-associated mesenchymal stem cells interact directly with tumor cells to promote metastasis of ovarian cancer. More specifically, our lab has shown that tetraspanins, (CD9, CD151, CD63, CD81) proteins with transmembrane domains and highly expressed on the surface of cells, may mediate these direct interactions. Based on these findings, it is hypothesized tetraspanins mediate direct interactions between tumor cells and cancer-associated mesenchymal stem cells to increase metastatic potential of ovarian cancer. To assess localization of tetraspanins in relation to tumor cells and cancer-associated mesenchymal stem cell, and to determine proximity of tetraspanins at cell contact points, a co-immunofluorescence (co-IF) staining and proximity ligation assay (PLA) was performed. Then, co-immunoprecipitation (co-IP) experiments were performed for further investigation of protein-protein interactions between tetraspanins.
The co-IF showed that cancer-associated mesenchymal stem cells express CD81 and CD63 while tumor cells mostly express CD9. Next, the PLA showed that (CD9-CD63) and (CD9-CD81) are in proximity at tumor cell and cancer-associated mesenchymal stem cell junctions. Further, CD63 and CD81 were detected after precipitating CD9 using the coIP. Taken together, these results indicate that CD9 directly binds to CD63 and CD81. Since direct interactions between cancer-associated mesenchymal stem cells and ovarian cancer cells are implicated in ovarian cancer metastasis, and these tetraspanins were shown to be upregulated on the surface of cancer-associated mesenchymal stem cells and tumor cells, tetraspanins may act as a causal agent in promoting lethality and metastasis of ovarian cancer.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
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| ETD Committee: |
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| Date: |
23 April 2021 |
| Date Type: |
Publication |
| Defense Date: |
24 March 2021 |
| Approval Date: |
23 April 2021 |
| Submission Date: |
22 April 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
38 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
David C. Frederick Honors College
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
BPhil - Bachelor of Philosophy |
| Thesis Type: |
Undergraduate Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
tumor microenvironment cancer-associated mesenchymal stem cell ovarian cancer |
| Date Deposited: |
23 Apr 2021 17:06 |
| Last Modified: |
23 Apr 2021 17:06 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40753 |
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Tetraspanin dependent tunneling nanotubule formation mediates stromal and cancer cell interactions, and facilitates ovarian cancer metastasis. (deposited 23 Apr 2021 17:06)
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