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E-cadherin promotes tumorigenicity in human ovarian surface epithelium Ong, Aldrich Dixon
Abstract
Ovarian cancer is the most lethal gynecological cancer in the Western world, but comparatively little is known about its development. Epithelial ovarian carcinomas are thought to originate in the ovarian surface epithelium (OSE), i.e. the mesothelium covering the ovary, but experimental evidence for this origin has been lacking. Contrary to most epithelia where neoplastic progression is associated with loss of E-cadherin, this cell-cell adhesion molecule is sparse in normal human OSE but its expression increases in ovarian epithelial metaplasia and neoplasia. Concurrently, the tumors tend to acquire characteristics of the complex epithelia of the oviduct and uterus. The high proportion of ovarian cancers where such aberrant Mullerian differentiation occurs suggests that this change may confer a selective advantage on the transforming cells. Previous studies in our laboratory showed that increased E-cadherin expression may be a cause of such Mullerian differentiation. E-cadherin was transfected into SV40 large T antigen-immortalized, E-cadherin-negative cells derived from normal OSE. Constitutive expression of E-cadherin re-established normal epithelial markers that had been lost in culture, such as keratin, and induced markers of metaplasia and neoplasia, such as CA125. In the present study, SV40-immortalized, E-cadherin-transfected cells, but not the E-cadherinnegative controls, were found to be anchorage independent and formed transplantable, invasive subcutaneous and intraperitoneal adenocarcinomas in 100% of injected SOD mice. Intraperitoneally injected tumor cells seeded the mesenteries and omentum, invaded the liver and thigh musculature, and produced ascites. The presence of SV40 large T antigen in the tumor cell nuclei confirmed their origin in the transfected OSE cells. This is the first experimental model of ovarian adenocarcinomas derived by genetic manipulations of normal human OSE. The results confirm the potential of OSE to give rise to ovarian epithelial carcinomas and suggest that upregulation of E-cadherin may play a pivotal role in their progression.
Item Metadata
Title |
E-cadherin promotes tumorigenicity in human ovarian surface epithelium
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1999
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Description |
Ovarian cancer is the most lethal gynecological cancer in the Western world, but
comparatively little is known about its development. Epithelial ovarian carcinomas are thought
to originate in the ovarian surface epithelium (OSE), i.e. the mesothelium covering the ovary, but
experimental evidence for this origin has been lacking. Contrary to most epithelia where
neoplastic progression is associated with loss of E-cadherin, this cell-cell adhesion molecule is
sparse in normal human OSE but its expression increases in ovarian epithelial metaplasia and
neoplasia. Concurrently, the tumors tend to acquire characteristics of the complex epithelia of the
oviduct and uterus. The high proportion of ovarian cancers where such aberrant Mullerian
differentiation occurs suggests that this change may confer a selective advantage on the
transforming cells. Previous studies in our laboratory showed that increased E-cadherin
expression may be a cause of such Mullerian differentiation. E-cadherin was transfected into
SV40 large T antigen-immortalized, E-cadherin-negative cells derived from normal OSE.
Constitutive expression of E-cadherin re-established normal epithelial markers that had been lost
in culture, such as keratin, and induced markers of metaplasia and neoplasia, such as CA125. In
the present study, SV40-immortalized, E-cadherin-transfected cells, but not the E-cadherinnegative
controls, were found to be anchorage independent and formed transplantable, invasive
subcutaneous and intraperitoneal adenocarcinomas in 100% of injected SOD mice.
Intraperitoneally injected tumor cells seeded the mesenteries and omentum, invaded the liver and
thigh musculature, and produced ascites. The presence of SV40 large T antigen in the tumor cell
nuclei confirmed their origin in the transfected OSE cells. This is the first experimental model of
ovarian adenocarcinomas derived by genetic manipulations of normal human OSE. The results
confirm the potential of OSE to give rise to ovarian epithelial carcinomas and suggest that
upregulation of E-cadherin may play a pivotal role in their progression.
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Extent |
5562113 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-06-26
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0088985
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1999-11
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.