In this dissertation, I examined the function of the alpha2beta1 integrin in epithelial tumor cells as well as in the tumor microenvironment. The alpha2beta1 integrin is a surface heterodimeric receptor found on epithelial, endothelial, fibroblasts, platelets, and several immune system cell subsets where it is responsible for cell-cell and cell-matrix interactions. Using the K14-HPV16 mouse model of inflammation-driven skin carcinogenesis on wild-type or alpha2beta1 integrin-null backgrounds, as well as an orthotopic murine breast cancer model, I elucidated the roles of this integrin during the multi-step progression towards cancer and eventual metastasis. My studies have implicated a role of the alpha2beta1 integrin in determining the growth and invasive behavior of tumor cells that is independent of the tumor microenvironment, yet influenced by the malignant cell type involved. My findings demonstrate an important function of the alpha2beta1 integrin on maintaining lymphatic vasculature integrity, thus providing novel insights into the function of this integrin in normal physiology as well as in tumor-associated lymphatics and metastasis. Through my examination of the multiple compartments known to drive cancer, it has been possible to ascertain this integrins contribution on the tumor cells, inflammatory cells, and additional cells of the tumor microenvironment towards mediating neoplastic progression and hematogenous as well as lymphatic metastasis.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12052011-233328 |
| Date | 12 December 2011 |
| Creators | Tran, Thuy Thanh Thi |
| Contributors | Larry Swift, Mary Zutter, Sarki Abdulkadir, Hal Moses, Jin Chen, Andries Zijlstra |
| 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-12052011-233328/ |
| 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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