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STUDIES OF MURINE PROSTATE CANCER STEM /
PROGENITOR CELLS
by
Chun-Peng Liao
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(BIOCHEMISTRY AND MOLECULAR BIOLOGY)
August 2008
Copyright 2008 Chun-Peng Liao
Object Description
| Title | Studies of murine prostate cancer stem / progenitor cells |
| Author | Liao, Chun-Peng |
| Author email | chunpenl@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Biochemistry & Molecular Biology |
| School | Keck School of Medicine |
| Date defended/completed | 2008-05-29 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-07-09 |
| Advisor (committee chair) | Roy-Burman, Pradip |
| Advisor (committee member) |
Frenkel, Baruch Dubeau, Louis |
| Abstract | The application of our prostate epithelium-specific Cre/loxP system to inactivate tumor suppressor genes had resulted in successful development of mouse models of prostate cancer. We further increased the efficiency of the conditional Pten deletion model of prostate adenocarcinoma by combining it with either a conditional luciferase or EGFP reporter line. The growth kinetics of the androgen dependent cancer (AD-Ca) and androgen-depletion independent recurrent cancer (ADI-Ca) could be followed non-invasively in live animals by bioluminescence imaging. We expect that such an investigation will be facilitated by timing the collection of tumorsat specific growth or re-growth points, an advantage that is provided by the model. The EGFP model can provide an opportunity to locate tumors or to isolate enriched populations of cancer cells from tumor tissues via fluorescence-based technologies. Previous studies have shown a small cell subpopulation with Lin-Sca-1+CD49f+ (LSC) cell surface marker phenotypes in the normal murine prostate to have the capacities of stemness. We examined the presence of such cells in our mouse models of prostate cancer, and found a much higher percentage of the LSC cellsubpopulation among the Lin- cells in AD-Ca and ADI-Ca compared to that in the proximal region of the normal counterparts.; To characterize the stemness abilities of cancer LSC cells, we conducted spheroid-forming analyses by the matrigel-based coculture system. Spheroids formed from the cancer LSC cells were larger than those form normal LSC cells. The spheroids could be passaged serially. In the presence of carcinoma associated fibroblasts, they showed a prostate cancer glandular-like structure. We also observed that only cancer LSC cells, not non-LSC, cells formed spheroids. The differentiation to various cell types in spheroids was identified by dual immunofluorescence staining. In the spheroids generated from normal LSC cells, CK8+ luminal cells were located in the intra-lumen layers, and p63+ basal cells in the outer layers. However, in the spheroids formed from cancer LSC cells, most of the cells in the inner layers are p63+CK8+ dual-positive indicating an intermediate phenotype. Taken together, these results describe the opportunity present in the model system to explore the role of stem cells in prostate cancer. |
| Keyword | prostate; cancer; stem; Cell; mouse; progenitor |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1326 |
| Rights | Liao, Chun-Peng |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Liao-20080709 |
| Archival file | uscthesesreloadpub_Volume32/etd-Liao-20080709.pdf |
Description
| Title | Page 1 |
| Full text | STUDIES OF MURINE PROSTATE CANCER STEM / PROGENITOR CELLS by Chun-Peng Liao A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (BIOCHEMISTRY AND MOLECULAR BIOLOGY) August 2008 Copyright 2008 Chun-Peng Liao |
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