Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target

  • Authors:
    • Tetsuyuki Takahashi
    • Hisanori Uehara
    • Keisuke Izumi
  • View Affiliations

  • Published online on: May 24, 2013     https://doi.org/10.3892/ijo.2013.1957
  • Pages: 416-424
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Abstract

We have previously reported that FuEP2/Ex2, a soluble decoy receptor for PGE2, suppresses tumor growth in an orthotopic xenograft model. To examine whether it has further uses, we examined the effect of FuEP2/Ex2 in an intraperitoneal metastasis model of ovarian cancer cells. We established FuEP2/Ex2-expressing ovarian cancer cells (SKOV/ip-FuEP2/Ex2) and injected them intraperitoneally into female nude mice. Mice injected with SKOV/ip-FuEP2/Ex2 had no ascitic fluid and showed smaller tumor lesions compared to mice injected with vector control cells, with decreased microvessel density and M2 macrophages. To identify molecular targets for combination treatment, we conducted cDNA microarray analysis and found three genes encoding enzyme [matrix metalloproteinase-7 (MMP-7), transmembrane protease serin 4 (TMPRSS4) and cytocrome P450 1B1 (CYP1B1)] to be upregulated in SKOV/ip-FuEP2/Ex2-derived tumors. Administration of TMPRSS4 inhibitor further reduced tumor weight and decreased the number of Ki-67‑positive cells in SKOV/ip-FuEP2/Ex2-injected mice. These data indicate a possible EP-targeting strategy using FuEP2/Ex2 in the treatment of ovarian cancer and suggest that dual targeting of EP-mediated signaling and TMPRSS4 may enhance therapeutic value.

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August 2013
Volume 43 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Takahashi T, Uehara H and Izumi K: Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target. Int J Oncol 43: 416-424, 2013
APA
Takahashi, T., Uehara, H., & Izumi, K. (2013). Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target. International Journal of Oncology, 43, 416-424. https://doi.org/10.3892/ijo.2013.1957
MLA
Takahashi, T., Uehara, H., Izumi, K."Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target". International Journal of Oncology 43.2 (2013): 416-424.
Chicago
Takahashi, T., Uehara, H., Izumi, K."Inhibitory effect of soluble EP2 receptor on ovarian tumor growth in nude mice and utility of TMPRSS4 as a combinatorial molecular target". International Journal of Oncology 43, no. 2 (2013): 416-424. https://doi.org/10.3892/ijo.2013.1957