Human Ovarian Surface Epithelial Cells Can Give Rise to Papillary Serous Carcinoma under the Influence of Specific Oncogenes and the Microenvironment
J Zheng, I Mercado-uribe, P Liu, DG Rosen, G Yang, A Malpica, H Naora, N Auersperg, GB Mills, RC Bast, J Liu. UT MD Anderson Cancer Center, Houston, TX; Shangdong Univ, Jinan, China; University of British Columbia, Vancouver, BC, Canada
Background: Several possible cell origins have been proposed for human ovarian cancer including ovarian surface epithelial cells, fallopian tube epithelia, and rete ovarii. However, data supporting such conclusions are largely from morphologic and genetic correlative evidence, a causal relationship between the cell origin and ovarian cancer has not been established.
Design: In this study, we determined whether human ovarian surface epithelial cells could be the origin of ovarian cancer by introducing genetic elements into normal human ovarian epithelial cells and test whether such genetic modifications can induce the development of ovarian cancer.
Results: Enforced expression of HER-2/neu into two nontumorigenic human ovarian surface epithelial cells previously immortalized with SV40 T/t antigen and the catalytic subunit of telomerase resulted in anchorage independent growth of these cells on soft agar. HER-2/neu transfected cells injected sub-cutaneously developed carcinoma with morphology resembling undifferentiated carcinomas (Fig 1F-G). However, when these tumor cells was injected into the peritoneal cavity of nude mice, one of two lines developed papillary carcinoma similar to high grade papillary serous carcinoma (Fig. 1A-E). The tumor cells are strongly positive for cytokeratin, WT-1, p53, and CA125 staining. Thus, this genetically created papillary carcinoma resembled high grade papillary serous carcinoma from patients by morphology and immunohistochemical criterias.
Conclusions: These results provide first casual genetic evidence that ovarian surface epithelial cells can serve as the origin of high grade serous carcinoma and that the development of papillary serous carcinoma is also dependent on the tumor microenvironment. This newly created ovarian cancer model should greatly facilitate the study of pathogenesis of human ovarian cancer.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 143, Wednesday Morning