Please use this identifier to cite or link to this item: https://doi.org/10.1002/ijc.25961
Title: The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer
Authors: Yamamura, S.
Matsumura, N.
Mandai, M.
Huang, Z.
Oura, T.
Baba, T.
Hamanishi, J.
Yamaguchi, K.
Kang, H.S.
Okamoto, T.
Abiko, K.
Mori, S. 
Murphy, S.K.
Konishi, I.
Keywords: metastasis
ovarian cancer
TGF β
Issue Date: 11-Jan-2012
Source: Yamamura, S., Matsumura, N., Mandai, M., Huang, Z., Oura, T., Baba, T., Hamanishi, J., Yamaguchi, K., Kang, H.S., Okamoto, T., Abiko, K., Mori, S., Murphy, S.K., Konishi, I. (2012-01-11). The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. International Journal of Cancer 130 (1) : 20-28. ScholarBank@NUS Repository. https://doi.org/10.1002/ijc.25961
Abstract: Peritoneal dissemination including omental metastasis is the most frequent route of metastasis and an important prognostic factor in advanced ovarian cancer. We analyzed the publicly available microarray dataset (GSE2109) using binary regression and found that the transforming growth factor (TGF)-beta signaling pathway was activated in omental metastases as compared to primary sites of disease. Immunohistochemical analysis of TGF-beta receptor type 2 and phosphorylated SMAD2 indicated that both were upregulated in omental metastases as compared to primary disease sites. Treatment of the mouse ovarian cancer cell line HM-1 with recombinant TGF-β1 promoted invasiveness, cell motility and cell attachment while these were suppressed by treatment with A-83-01, an inhibitor of the TGF-β signaling pathway. Microarray analysis of HM-1 cells treated with TGF-β1 and/or A-83-01 revealed that A-83-01 efficiently inhibited transcriptional changes that are induced by TGF-β1. Using gene set enrichment analysis, we found that genes upregulated by TGF-β1 in HM-1 cells were also significantly upregulated in omental metastases compared to primary sites in the human ovarian cancer dataset, GSE2109 (false discovery rate (FDR) q = 0.086). Therapeutic effects of A-83-01 in a mouse model of peritoneal dissemination were examined. Intraperitoneal injection of A-83-01 (150 μg given three times weekly) significantly improved survival (p = 0.015). In summary, these results show that the activated TGF-β signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. Copyright © 2011 UICC.
Source Title: International Journal of Cancer
URI: http://scholarbank.nus.edu.sg/handle/10635/116623
ISSN: 00207136
DOI: 10.1002/ijc.25961
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