Progression to castrate resistant prostate cancer (CRPC) is associated with high morbidity. Disease recurrence and progression is influenced by the tumor microenvironment. Resident and recruited stroma contribute to cancer progression through paracrine signaling. A conditional stromal TGF-beta type II receptor knockout mouse model (Tgfbr2fspKO) was characterized to be a model for understanding CRPC progression. We demonstrated the resident stromal fibroblast responsiveness to TGF-beta mediated paracrine canonical Wnt signaling in the adjacent prostate epithelia in castrate resistance. Regrowth of the prostate was associated with recruitment of stromal cells from the bone marrow and a contributor to CRPC. We determined that a population of bone marrow derived cells, particularly the mesenchymal stem cells (MSCs), were recruited and fused to prostatic ductal epithelia. These MSCs were found to be a source of Wnt ligands that could contribute to castrate resistant prostatic epithelia. In summary, the tumor microenvironment composed of both resident and recruited stromal cells mediate CRPC through paracrine signaling.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-09092010-103609 |
| Date | 22 September 2010 |
| Creators | Placencio, Veronica Rae Padilla |
| Contributors | Jeffrey M. Davidson, Harold L. Moses, Robert J. Matusik, Neil A. Bhowmick |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-09092010-103609/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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