Impact of the Ovarian Microenvironment on Serous Cancer
Technical Report,01 Aug 2015,31 Jul 2016
University of Illinois at Chicago Chicago United States
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Many now believe that the fallopian tube epithelium is the progenitor cell type for high-grade serous ovarian carcinoma. The initial phase of tubal cell metastasis could involve several sets of molecules, each of which represents a possible therapeutic target for intervention that would block serous cancer while still confined to the fallopian tubes. Using a series of normal, modified, and tumorigenic tubal cell lines, we will investigate the properties that allow tubal cells to migrate and adhere to novel three-dimensional ovarian organ cultures. We will also determine if the ovarian factors are necessary to fully transform fallopian tube cells. Using these as experimental models of pathway-modified or tumorigenic cells of tubal origin, we will investigate if ovarian factors enhance migration as a mechanism to explain the presence of tumor mass in the ovary of serous patients. 3D ovarian organ culture conditioned medium will be used as the chemo-attractant. Collagen is a well-established matrix utilized by serous cancer cells, of unknown origin, to seed metastatic sites, such as the mesothelium. An RNAseq analysis will be performed between human TEC adhered to collagen matrix compared to tissue culture plastic and used to identify gene expression changes responsible for adhesion on collagen. Ovarian conditioned medium OCM with and without H2O2treatment will be added to normal and our series of pathway-modified oviductal cell lines to determine if proliferation and growth in soft agar are enhanced by factors in the OCM.