Tumor Necrosis Factor-α-Induced Matrix Proteolytic Enzyme Production and Basement Membrane Remodeling by Human Ovarian Surface Epithelial CellsMolecular Basis Linking Ovulation and Cancer Risk
The majority of cancer is of surface/cyst epithelial origin. The ovarian surface epithelial cells are organized by a sheet of basement membrane composed mainly of collagen IV and laminin, and it is believed that the basement membrane greatly influences the physiological properties of ovarian surface epithelial cells. Previous studies in our laboratories indicated that loss of the basement membrane, an obligated step in ovulation, is also a critical step during the morphological transformation and tumor initiation of the ovarian surface epithelium. It is speculated that the loss of basement membrane in ovarian surface epithelial transformation may have similar biological mechanism to the loss of surface epithelial basement membrane in ovulation. However, the mechanisms involved in the ovarian surface epithelial basement membrane removal during ovulation are still not completely understood. In the current study, cultured human ovarian surface epithelial (HOSE) cells were examined for their abilities to produce matrix hydrolyzing enzymes and degrade basement membrane in response to a number of potential local mediators in ovulation. Among the candidate-stimulating factors tested, tumor necrosis factor (TNF)-alpha and IL-1beta (to a lesser extent) were found to drastically increase urokinase type plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 activities secreted from HOSE cells. MMP-2, the other major HOSE cell-secreted gelatinase, is constitutively produced but not regulated. As demonstrated by immunofluorescence staining and Western blot analysis, TNF-alpha treatment caused the degradation and structural reorganization of collagen IV and laminin secreted and deposited by HOSE cells in culture. Amiloride, an uPA inhibitor, not only inhibited the activity of uPA but was also able to suppress TNF-alpha-stimulated MMP-9 activity and prevented the TNF-alpha-stimulated remodeling of the basement membrane extracellular matrix, suggesting the contribution of uPA-mediated proteolytic cascade in this process. This study implicates the potential roles of TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement membrane degradation and remodeling, which are processes during ovulation and may contribute to epithelial transformation. The findings may underscore the importance of TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement membrane remodeling and may provide a molecular mechanism linking ovulation and ovarian cancer risk.
Pharmacology, Toxicology and Pharmaceutical Science
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Engineering
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Other
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Unknown
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Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 February 2014.
All research outputs
#7,646,787
of 28,840,878 outputs
Outputs from Cancer Research
#7,650
of 21,095 outputs
Outputs of similar age
#23,638
of 71,272 outputs
Outputs of similar age from Cancer Research
#123
of 244 outputs
Altmetric has tracked 28,840,878 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 21,095 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one has gotten more attention than average, scoring higher than 62% of its peers.
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We're also able to compare this research output to 244 others from the same source and published within six weeks on either side of this one. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
