Dataset Information

Hematogenous metastasis of ovarian cancer: rethinking mode of spread.

ABSTRACT: 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-neuregulin 1 (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 impaired omental metastasis. Our results highlight hematogenous metastasis as an important mode of ovarian cancer metastasis. These findings have implications for designing alternative strategies aimed at preventing and treating ovarian cancer metastasis.

SUBMITTER: Pradeep S

PROVIDER: S-EPMC4100212 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Hematogenous metastasis of ovarian cancer: rethinking mode of spread.

Pradeep Sunila S Kim Seung W SW Wu Sherry Y SY Nishimura Masato M Chaluvally-Raghavan Pradeep P Miyake Takahito T Pecot Chad V CV Kim Sun-Jin SJ Choi Hyun Jin HJ Bischoff Farideh Z FZ Mayer Julie Ann JA Huang Li L Nick Alpa M AM Hall Carolyn S CS Rodriguez-Aguayo Cristian C Zand Behrouz B Dalton Heather J HJ Arumugam Thiruvengadam T Lee Ho Jeong HJ Han Hee Dong HD Cho Min Soon MS Rupaimoole Rajesha R Mangala Lingegowda S LS Sehgal Vasudha V Oh Sang Cheul SC Liu Jinsong J Lee Ju-Seog JS Coleman Robert L RL Ram Prahlad P Lopez-Berestein Gabriel G Fidler Isaiah J IJ Sood Anil K AK

Cancer cell 20140701 1

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-neuregulin 1 (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 t ...[more]

PMID: 25026212

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Project description:Two groupsHepatocellular carcinoma (HCC) is a heterogeneous malignant disease with molecularly and clinically distinct subtypes discovered in genomic studies. Mouse models are commonly used as preclinical model to study hepatocarcinogenesis, but how well these models recapitulate molecular subtypes of human HCC is unclear. Thus, we aimed to correlate nine mouse HCC models with clinical subtypes of human HCC by systematically comparing their genomic data. By integrating nine molecularly and clinically defined genomic signatures for human HCC with genomic data from nine mouse HCC models, we identified the mouse models that best resembled subtypes of human HCC and determined the clinical relevance of each model. Mst1/2 KO, Sav1 KO, and SV40 T antigen mouse model best recapitulated poor prognostic subtypes of human HCC, whereas the Myc transgenic model best resembled human HCCs with more favorable prognoses. The Myc model was also significantly associated with activation of β-catenin. E2f1, E2f1/Myc, E2f1/Tgfa, and diethylnitrosamine (DENA)-induced models were heterogeneous and were unequally split to poor and favorable prognoses. Most interestingly, Mst1/2 KO and Sav1 KO models best resembles human HCC with hepatic stem cell characteristics. When we applied a genomic predictor for immunotherapy, the six-gene interferon-γ (IFNG6) score, Mst1/2 KO, Sav1 KO, SV40, and DEN models were predicted to be the least responsive to immunotherapy. Further analysis of immune checkpoint genes showed that high expression of immune inhibitory genes (Cd276 and Pvrl2) in Mst1/2 KO, Sav1 KO, SV40 and low expression of immune stimulatory genes (Cd86) in DENA model might be accountable for lack of predictive response to immunotherapy. Conclusion: Most of the mouse models effectively recapitulated molecular characteristics of human subtypes, including response to immunotherapy. of samples are included: 1.SKOV3-ip1 2.SKOV3-OM3. Gene expression profiles of SKOV3-OM3 cells were compared to that of parental SKOV3 ip1 cells.

Dataset Information

Hematogenous metastasis of ovarian cancer: rethinking mode of spread.

Publications

Hematogenous metastasis of ovarian cancer: rethinking mode of spread.

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