Sheep stromal‐epithelial cell interactions and ovarian tumor progression

Previous studies suggest that underlying ovarian stromal cues may regulate the ovarian surface epithelium. However, little is known about the interaction between ovarian stromal cells (OSC) and ovarian surface epithelial cells (OSE) under normal physiologic and pathologic conditions, largely because...

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Published in:International journal of cancer 2007-11, Vol.121 (10), p.2346-2354
Main Authors: Wang‐Johanning, Feng, Huang, Miao, Liu, Jinsong, Rycaj, Kiera, Plummer, Joshua B., Barnhart, Kirstin F., Satterfield, William C., Johanning, Gary L.
Format: Article
Language:English
Subjects:
Animal tumors. Experimental tumors
Animals
Antigens, Polyomavirus Transforming - metabolism
Biological and medical sciences
Cell Transformation, Neoplastic - pathology
Cells, Cultured
Disease Progression
Epithelial Cells - metabolism
Experimental genital and mammary tumors
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Medical sciences
Mice
Mice, Nude
ovarian cancer
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
ovarian surface epithelia
ras Proteins - metabolism
Sheep
sheep ovarian stromal cells
Stromal Cells - metabolism
stromal‐epithelial cell interactions
Telomerase - metabolism
transformed sheep ovarian stromal cells
Tumors
Xenograft Model Antitumor Assays
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Summary:Previous studies suggest that underlying ovarian stromal cues may regulate the ovarian surface epithelium. However, little is known about the interaction between ovarian stromal cells (OSC) and ovarian surface epithelial cells (OSE) under normal physiologic and pathologic conditions, largely because of the lack of a suitable model. In the current study, the OSC obtained from a sheep were immortalized with SV‐40 T/t antigen (designated IOSC) and telomerase reverse transcriptase (designated IOSCH), followed by transfection with the oncogenic allele of the human H‐Ras oncogene (designated IOSChR). IOSC cells transfected with H‐Ras before immortalization with telomerase were designated IOSCRH. These sheep OSCs were used in both in vitro and in vivo model systems to evaluate mechanisms by which OSCs influence ovarian tumor progression. Normal sheep OSCs were found to inhibit the growth of SKOV3 and OVCAR3 human ovarian cancer cells, but not normal sheep OSE and human OSE cells (hOSE137 cells). In contrast, IOSChR and IOSCRH cells stimulated the growth of normal sheep and human OSE cells, as well as cancer cells. These findings were confirmed by in vivo studies. Our data provide compelling support for the importance of stromal‐epithelial cell interactions during tumor progression, and show for the first time that immortalized and transformed OSCs promote growth of ovarian epithelial tumors. © 2007 Wiley‐Liss, Inc.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.22960