Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2

  • Authors:
    • Shin-Ichi Nakanuma
    • Hidehiro Tajima
    • Kouichi Okamoto
    • Hironori Hayashi
    • Hisatoshi Nakagawara
    • Ichiro Onishi
    • Hiroyuki Takamura
    • Hirohisa Kitagawa
    • Sachio Fushida
    • Takashi Tani
    • Takashi Fujimura
    • Masato Kayahara
    • Tetsuo Ohta
    • Tomohiko Wakayama
    • Shoichi Iseki
    • Shin-Ichi Harada
  • View Affiliations

  • Published online on: April 1, 2010     https://doi.org/10.3892/ijo_00000555
  • Pages: 793-800
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic cholangiocarcinoma (ICC) specimens, but absent in hepatocellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts.

Related Articles

Journal Cover

April 2010
Volume 36 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Nakanuma S, Tajima H, Okamoto K, Hayashi H, Nakagawara H, Onishi I, Takamura H, Kitagawa H, Fushida S, Tani T, Tani T, et al: Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2. Int J Oncol 36: 793-800, 2010
APA
Nakanuma, S., Tajima, H., Okamoto, K., Hayashi, H., Nakagawara, H., Onishi, I. ... Harada, S. (2010). Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2. International Journal of Oncology, 36, 793-800. https://doi.org/10.3892/ijo_00000555
MLA
Nakanuma, S., Tajima, H., Okamoto, K., Hayashi, H., Nakagawara, H., Onishi, I., Takamura, H., Kitagawa, H., Fushida, S., Tani, T., Fujimura, T., Kayahara, M., Ohta, T., Wakayama, T., Iseki, S., Harada, S."Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2". International Journal of Oncology 36.4 (2010): 793-800.
Chicago
Nakanuma, S., Tajima, H., Okamoto, K., Hayashi, H., Nakagawara, H., Onishi, I., Takamura, H., Kitagawa, H., Fushida, S., Tani, T., Fujimura, T., Kayahara, M., Ohta, T., Wakayama, T., Iseki, S., Harada, S."Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2". International Journal of Oncology 36, no. 4 (2010): 793-800. https://doi.org/10.3892/ijo_00000555