Enhancement Of Adhesion To Extracellular Matrix By Glucocorticoid In Human Ovarian Cancer Cells And Its Potential Mechanisms

Ninety percent of ovarian cancer arises from the ovarian surface epithelium (OSE) with a high mortality rate in the common gynecologic malignant tumor. Due to the complex of biological characteristics and pathological types, the development mechanism of ovarian cancer is still not clear. Steroid hormone plays an important role in regulation of the cell biological events. The rate of glucocorticoid receptor (GR) existence is higher than that of estrogen receptor and progesterone receptor in ovarian cancer cells, which prompts glucocorticoid may involve in ovarian cancer development process. However, the effect of glucorcoticoid (GC) on epithelial ovarian function is not known so much. During our previous study, synthetic glucocorticoid-dexamethasone (Dex) can lead to pronounced morphologic alteration and the enhancement of adhesion to ECM in a human ovarian cancer cell line HO-8910 which expresses GR. We have got the similar result in another human ovarian cancer cell line SKOV3. During the next work, we found Dex could up-regulate the expression of integrinα4β1 andαVβ1, which related to the promotion of cell adhesion by Dex in HO-8910. Based on the above results, we want to know the effect of Dex on ECM expression and secretion in this process, and further, whether EMT (epithelial-mesenchymal transition) occurs during this process in HO-8910. The study is facilitated to know the effect of Dex on adhesion in ovarian cancer cells and the development of the ovarian cancer.Mainly with the methods of Real-time PCR,Western Blot and ELISA, we found that 100nM Dex could significantly induce the expression and secretion of many ECM components:1) Dex up-regulates the expression and secretion of collagen. It increases the collagen typeⅠand typeⅢmRNA expression and induce the secretion of collagen typeⅢand typeⅣ.2) Dex induces the secretion of noncollagen protein-Laminin.3) Dex induces the secretion of Hyaluronan. The above results suggest that Dex can significantly increase the expression and secretion of ECM components to promote cell adhesion.We also found morphologic alteration (irregular epithelial type into fibrous) with the treatment of Dex. Using immunofluorescence stain and confocal microscopy to observe the effect of 100nM Dex on cytoskeleton-actin, we have observed that Dex can promote the reconstruction of cytoskeleton and the formation of stress fiber. Meanwhile, Dex can rapidly increase the level of tyrosine phosphorylation of FAK (focal adhesion kinase) without a change in protein expression. In consideration of the morphologic alteration and inducement of ECM, we wonder whether Dex promotes the occurrence of EMT. We detected the effect of 100nM Dex on Slug and Twist expression which are significant transcription factors in EMT. We found that Dex could increase the expression of Slug in both mRNA and protein level but not regulate that of Twist.To sum up, Dex can induce expression and secretion of various ECM components, promote the reconstruction of cytoskeleton and increase the level of tyrosine phosphorylation of FAK to enhance the adhesion ability in HO-8910 cells. Also, it leads to morphologic alteration, increases the expression and secretion of ECM and induces the expression of EMT related transcription factor-Slug, which prompts it may promote the occurrence of EMT.