Project description:ETS1 expression is induced by the microenvironment of ovarian metastasis and this expression allows ETS1 to activate a gene expression program involved in cell invasion and epithelial mesenchymal transision.
Project description:ETS1 expression is induced by the microenvironment of ovarian metastasis and this expression allows ETS1 to activate a gene expression program involved in cell invasion and epithelial mesenchymal transision.
Project description:Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported cancer cell viability during nutrient and isolation stress and enabled prolonged proliferation. Co-culturing with pre-adipocytes led to upregulation of genes involved in extracellular matrix (ECM) organization, cellular response to stress, and regulation of insulin-like growth factor (IGF) signaling in ovarian cancer cells. IGF-1 induced ECM genes and increased alternative NF-κB signaling by activating RelB. Inhibiting the IGF-1 receptor (IGF1R) initially increased tumor omental adhesion but decreased growth of established preadipocyte-induced subcutaneous tumors as well as established intraperitoneal tumors. Together, this study shows that omental preadipocytes support ovarian cancer progression, which has implications for targeting metastasis.
Project description:Matched high-grade serous ovarian carcinoma samples collected from the ovary (ov), omental metastasis (om-met), and non-omental intraperitoneal metastasis (met) from 10 patients at the time of primary debulking surgery were analyzed for RNA expression by RNA sequencing.
Project description:To determine the role of the hepatic microenvironment in HCC metastasis, we compared the gene expression profiles of 20 noncancerous surrounding hepatic tissues from two HCC patient groups, those with primary HCC together with venous metastasis which we termed a metastasis-inclined microenvironment (MIM) and those with HCC without detectable metastasis, which we termed a metastasis-averse microenvironment (MAM). There were a total of 20 cDNA microarrays performed, comparing 9 MIM or 11 MAM HCC patient samples to a common reference pool of 8 normal liver tissues.
Project description:To determine the role of the hepatic microenvironment in HCC metastasis, we compared the gene expression profiles of 20 noncancerous surrounding hepatic tissues from two HCC patient groups, those with primary HCC together with venous metastasis which we termed a metastasis-inclined microenvironment (MIM) and those with HCC without detectable metastasis, which we termed a metastasis-averse microenvironment (MAM). Keywords: disease state design
Project description:Ovarian cancer has a clear predilection for metastasis to the omentum, but the underlying mechanisms involved in ovarian cancer spread are not well understood. Here, we used a parabiosis model that demonstrates preferential hematogenous metastasis of ovarian cancer to the omentum. Our studies revealed that the ErbB3-neuregulin1 (NRG1) axis is a dominant pathway responsible for hematogenous omental metastasis. Elevated levels of ErbB3 in ovarian cancer cells and NRG1 in the omentum allowed for tumor cell localization and growth in the omentum. Depletion of ErbB3 in ovarian cancer substantially impaired omental metastasis. Our results highlight hematogenous metastasis as a previously under-recognized mode of ovarian cancer metastasis. These findings have implications for designing new strategies aimed at preventing and treating ovarian cancer metastasis.