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STUDY OF BONE MORPHOGENETIC PROTEIN-2 AND STROMAL CELL
DERIVED FACTOR-1 IN PROSTATE CANCER
by
Azadeh Fata
__________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR AND EXPERIMENTAL PATHOLOGY)
May 2012
Copyright 2012 Azadeh Fata
Object Description
| Title | Study of bone morphogenetic protein-2 and stromal cell derived factor-1 in prostate cancer |
| Author | Fata, Azadeh |
| Author email | azfata@gmail.com;azfata@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2012-05-03 |
| Date submitted | 2012-05-06 |
| Date approved | 2012-05-06 |
| Restricted until | 2012-05-06 |
| Date published | 2012-05-06 |
| Advisor (committee chair) | Kalra, Vijay |
| Advisor (committee member) |
Widelitz, Randall B. Roy-Burman, Pradip |
| Abstract | The focus of this study is to better understand the role of bone morphogenetic protein-2 (BMP-2), and stromal cell-derived factor-1 (SDF-1) that occur in the prostate cancer tumor microenvironment with respect to interactions between malignant epithelial cells and the associated fibroblastic cells. The research concerns two distinct phases of the disease: androgen-dependent primary tumor (AD cancer) and the post-castration androgen refractory tumor development-the castration resistant prostate cancer (CRPC). The model systems used are E8 (primary tumor), and cE1 (CRPC tumor) malignant epithelial cell lines, and primary cultures of cancer-associated fibroblasts, derived from primary tumor (AD-CAFs) or CRPC tumor (CRPC-CAFs). All cellular materials have a homologous origin from the conditional Pten deletion mouse model of prostate cancer. First, it is shown that all CAFs, AD or CRPC in origin, are responsive to BMP-2 induced stimulation of SDF-1 expression. While the level of induction varies from one AD-CAF to another, a single CRPC-CAF tested exhibits a robust induction of SDF-1 by BMP-2. Second, the constitutive level of secreted SDF-1 is significantly higher in CRPC-CAF as compared to AD-CAFs. In contrast to these observations on SDF-1 induction, the levels of the cognate receptor CXCR4 appears to be low in CRPC cancer cells (cE1) in relation to that in primary tumor cells (E8). This opposite spectrum of ligand and receptor expression may, perhaps, be a mode of operation to regulate tumor growth in the prostate tumor microenvironment. Third, the increased level of CXCR4 in E8 cells is demonstrated to correlate well with their responsiveness to SDF-1 for proliferation or migration potentials. Finally, it is possible that the high levels of SDF-1 produced by CRPC-CAFs may have other significant role, such as, in cancer cell invasion and tumor angiogenesis that are critical for the recurrent tumor growth and metastasis. These clues; however, remain to be better developed in the future. ❧ Taken together this report sets-up a new oncogenic property of BMP-2- SDF-1 axis in two different types of the prostate tumors, the primary and the recurrent prostate cancer, introducing an interesting aspect of heterotypic cell interaction potentially critical in prostate cancer. |
| Keyword | androgen-dependent primary tumor (AD cancer); castration resistant prostate cancer (CRPC); bone morphogenetic protein-2; malignant epithelial cells; malignant fibroblastic cells; prostate cancer; tumor microenvironment; stromal cell derived factor-1 |
| 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 |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m |
| Rights | Fata, Azadeh |
| Access conditions | The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the author, as the original true and official version of the work, but does not grant the reader permission to use the work if the desired use is covered by copyright. It is the author, as rights holder, who must provide use permission if such use is covered by copyright. The original signature page accompanying the original submission of the work to the USC Libraries is retained by the USC Libraries and a copy of it may be obtained by authorized requesters contacting the repository e-mail address given. |
| Repository name | University of Southern California Digital Library |
| Repository address | USC Digital Library, University of Southern California, University Park Campus MC 7002, 106 University Village, Los Angeles, California 90089-7002, USA |
| Repository email | cisadmin@usc.edu |
| Archival file | uscthesesreloadpub_Volume4/etd-FataAzadeh-791.pdf |
Description
| Title | Page 1 |
| Full text | STUDY OF BONE MORPHOGENETIC PROTEIN-2 AND STROMAL CELL DERIVED FACTOR-1 IN PROSTATE CANCER by Azadeh Fata __________________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (MOLECULAR AND EXPERIMENTAL PATHOLOGY) May 2012 Copyright 2012 Azadeh Fata |
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