Estrogen Promotes Proliferation And Apoptosis Of Endometrial Carcinoma Cell Lines Ishikawa And Hec1a Via Endometrial Stromal Cells

Endometrial carcinoma is the leading malignancies of women in Western countries and the second leading cancer of female in China. As endometrial stromal cells (ESCs) are sharply decreased in endometrial carcinoma (EC) compared to normal endometrium, it is interested to explore the roll of ESCs in the tumorigenesis of endometrium. Unopposed estrogen is considered as the etiology of endometrioid carcinoma, but the underlying mechanism is needed to further explore. This study is to determine the biological effects of primary cultured ESCs on two endometrial cancer cell lines-Ishikawa and HEC1A. ESCs from normal, atypical hyperplastic and malignant endometrial specimens were collected, validated by immunohistochemistry and cultured in vitro, which were maintained in a medium containing 10 nM estradiol (E 2 ) for three months to simulate the unopposed estrogen stimulation of EC patients. Microarray were performed to detect the alteration of gene expression, which were then confirmed by real time RT-PCR. Co-culture of ESC and EC cell lines were performed by Transwell plate. Cell proliferation was analyzed by CCK8 assay. Apoptosis was analyzed by flow cytometry based on PI/Anexin V staining. Our results showed E 2 promoted the proliferation of three types of ESCs. E 2 has no direct effect on cancer cell lines Ishikawa and HEC1A, but when they co-cultured with ESCs, which were stimulated by E2, the proliferation of cancer cells was promoted by all three type of ESCs. Moor interestedly, we found that the much obvious promoted effects were occurred by the ESCs that extracted from malignant samples. Estrogen could also reduce the apoptosis of both cancer cell lines when co-culturing with ESCs from normal specimen. Gene microarray and real time RT-PCR indicated that collagen 9 were up-regulated 2.3 times when ESCs cells treated by E 2 . In conclusion, Estrogen altered the microenvironment of stromal cells, which could lead to the proliferation of endometrial carcinoma cells via paracrine function. The alteration of collagen synthesis by ESCs might contribute to this communication between the epithelial and mesenchymal cells. Citation Format: Xiang Tao, Jian Wu, Yinhua Yu. Estrogen promotes proliferation and apoptosis of endometrial carcinoma cell lines Ishikawa and HEC1A via endometrial stromal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4324. doi:10.1158/1538-7445.AM2017-4324