| Background:With epithelial ovarian cancer as the most common type, ovarian cancer has the highest rate of mortality in gynecological malignancies. Two major factors account for the dilemma existed in ovarian cancer treatment-late diagnosis and metastatic recurrence. Compared with primary tumors, cells in the metastatic location possess a specific pattern of genes expression and usually become refractory to clinical treatments. To better improve the prognosis of ovarian cancer, effective therapy for inhibition and elimination of metastasis is needed.Object:To establish an optimal mouse model for the research of ovarian cancer metastasis, and acquire the sub-clones with higher organotropic metastasis potential; screening for specific genes in association with tumors organotropic metastasis and providing molecular targets for clinical treatment of metastasis.Methods:The lentivirus-mediated gene transfer system was used to establish a specific cell line SKOV3-Luciferase/RFP, with the co-expression of two reporter genes luciferase and RFP. The growth and metastasis of tumor cells were observed with the in vivo image system. Differences in genes expression levels were detected by the gene chip technology and the results were tested by the RT-PCR, western blot analysis and immunohistochemistry assays.Results:The dissemination process of ovarian cancers from primary sites to other places could be simulated in our model. Sub-clones with relative higher metastasis potential to peritoneal and lung were selected through in vivo experiments. These sub-clones displayed notable features in metastasis to specific organs and significant differences were found in their genes expressions. The functions of altered genes in the S-cells are focused on cells proliferation, motility and metabolism regulation as well as angiogenesis promoting. While those in the L-cells are mainly focused on maintaining the homeostasis of stem cells and regulations of immuno-responses.Conclusions:We have established an optimal "primary-metastasis" mouse model with good stability and reliability. Besides, we have established several sub-clones with higher organotropic metastasis potential. Different expression signatures of the peritoneal and lung derived sub-clones indicated that organotropic metastasis related genes might help clones survival in distant organs. Therapies target these genes functions may help improve the therapeutic effects of current clinical treatment on ovarian cancer through inhibition of metastasis. |
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