Age-Related Expression of PEDF/EPC-1 in Human Endometrial Stromal Fibroblasts: Implications for Interactive Senescence

Aging is the major risk factor for many cancers, and age-related changes in the tissue microenvironment can facilitate tumor growth. This study uses human endometrial cells to begin to test the hypothesis that age-related changes in pigment epithelium-derived factor/early population doubling cDNA-1...

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Bibliographic Details
Published in:Experimental cell research 1999-02, Vol.247 (1), p.142-147
Main Authors: Palmieri, Diane, Watson, Joanna M., Rinehart, Clifford A.
Format: Article
Language:English
Subjects:
Adult
Antineoplastic Agents - pharmacology
Cellular Senescence - physiology
Endometrial Neoplasms - pathology
Endometrium - cytology
Endometrium - metabolism
Eye Proteins
Female
Fibroblasts - metabolism
Growth Inhibitors - physiology
Humans
Nerve Growth Factors
Protein Biosynthesis
Proteins - physiology
RNA, Messenger - metabolism
Serpins - biosynthesis
Serpins - physiology
Stromal Cells - metabolism
Tumor Cells, Cultured
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Summary:Aging is the major risk factor for many cancers, and age-related changes in the tissue microenvironment can facilitate tumor growth. This study uses human endometrial cells to begin to test the hypothesis that age-related changes in pigment epithelium-derived factor/early population doubling cDNA-1 (PEDF/EPC-1) levels create an environment that is more permissive to tumor growth. Endometrial stromal fibroblasts (ESF) are the predominant cell type in the human endometrium and exert regulatory control over the glandular epithelial cells, which are the source of most tumors. As ESF agein vitro,their ability to regulate appropriate growth and differentiation of epithelial cells declines. Endometrial epithelial cells in primary culture expressed relatively low levels of PEDF/EPC-1 mRNA. In contrast, early passage quiescent ESF from adult donors produce higher levels of the 1.5-kb PEDF/EPC-1 mRNA and 50-kDa secreted protein than epithelial cells. As ESF agein vitrothe relative abundance of PEDF/EPC-1 mRNA declines, as does the level of PEDF/EPC-1 protein secreted into cell culture medium. Treatment with PEDF/EPC-1 protein had no effect on ESF proliferation but did inhibit anchorage-dependent and anchorage-independent proliferation of endometrial carcinoma cells in a dose- and time-dependent manner. These findings imply that an age-related loss of PEDF/EPC-1 expression by ESF could eliminate a negative regulator of cancer cell growth and, thereby, contribute to the age-related increase in cancer incidence.
ISSN:0014-4827
1090-2422
DOI:10.1006/excr.1998.4341