Intravital imaging of metastasis in zebrafish
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018.
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| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2018
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| Online Access: | http://hdl.handle.net/1721.1/117867 |
| _version_ | 1811079481447677952 |
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| author | Benjamin, David Colin |
| author2 | Richard 0. Hynes. |
| author_facet | Richard 0. Hynes. Benjamin, David Colin |
| author_sort | Benjamin, David Colin |
| collection | MIT |
| description | Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018. |
| first_indexed | 2024-09-23T11:15:43Z |
| format | Thesis |
| id | mit-1721.1/117867 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T11:15:43Z |
| publishDate | 2018 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1178672019-04-12T23:22:09Z Intravital imaging of metastasis in zebrafish Benjamin, David Colin Richard 0. Hynes. Massachusetts Institute of Technology. Department of Biology. Massachusetts Institute of Technology. Department of Biology. Biology. Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018. DVD-ROM contains: movies/videos. Cataloged from PDF version of thesis. Includes bibliographical references. Metastasis is the cause of the overwhelming majority of cancer deaths. However, it remains a poorly understood process. The events at the metastatic site are especially poorly comprehended. These events are dynamic and so require intravital imaging to investigate. However, the intravital imaging of these events in mice is challenging. Sites of metastasis are often in vital organs that are inaccessible to microscopy without surgical intervention. Furthermore, circulating tumor cells are rare and are involved in many transient interactions adding to the challenge. The development of a line of zebrafish, Casper, that is transparent throughout its life suggested that zebrafish might be a powerful system for intravital imaging. I first developed novel injection and imaging techniques to study metastasis through intravital imaging in adult zebrafish. I then followed individual ZMEL1 zebrafish melanoma cells at the metastatic site over the course of two weeks as they grew from single disseminated tumor cells into macroscopic metastases. From these studies, I characterized the steps of metastasis at the metastatic site for this cell line. I also utilized transparent zebrafish embryos to uncover a new role for the oncogene YAP during metastasis. I observed that the over-expression of a Hippo-insensitive mutant of YAP (YAP-AA) promoted brain metastasis following intravenous in zebrafish embryos. I determined that YAP-AA was promoting tumor cell dispersal throughout the embryo by allowing tumor cells to escape the first capillary bed they encounter. Following intravenous injection, control cells lodge in blood vessels in the tail and cease their travel through circulation. However, YAP-AA cells are able to move through these vessels, re-enter circulation and travel to other organs, such as the brain. These observations represent a new mechanism by which tumor cells can increase their dissemination throughout an animal. by David Colin Benjamin. Ph. D. 2018-09-17T15:47:46Z 2018-09-17T15:47:46Z 2018 2018 Thesis http://hdl.handle.net/1721.1/117867 1051190149 eng System requirement: DVD-ROM drive. MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 255 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Benjamin, David Colin Intravital imaging of metastasis in zebrafish |
| title | Intravital imaging of metastasis in zebrafish |
| title_full | Intravital imaging of metastasis in zebrafish |
| title_fullStr | Intravital imaging of metastasis in zebrafish |
| title_full_unstemmed | Intravital imaging of metastasis in zebrafish |
| title_short | Intravital imaging of metastasis in zebrafish |
| title_sort | intravital imaging of metastasis in zebrafish |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/117867 |
| work_keys_str_mv | AT benjamindavidcolin intravitalimagingofmetastasisinzebrafish |