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Article

Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts

  • Authors:
    • Shin Takesue
    • Kenoki Ohuchida
    • Tomohiko Shinkawa
    • Yoshiki Otsubo
    • Sokichi Matsumoto
    • Akiko Sagara
    • Akiko Yonenaga
    • Yohei Ando
    • Shin Kibe
    • Hiromichi Nakayama
    • Chika Iwamoto
    • Koji Shindo
    • Taiki Moriyama
    • Kohei Nakata
    • Yoshihiro Miyasaka
    • Takao Ohtsuka
    • Hiroki Toma
    • Yohei Tominaga
    • Kazuhiro Mizumoto
    • Makoto Hashizume
    • Masafumi Nakamura
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan, Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan, Department of Endoscopic Diagnostics and Therapeutics, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan
  • Pages: 596-605
    |
    Published online on: December 24, 2019
       https://doi.org/10.3892/ijo.2019.4951
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Abstract

Cancer‑associated fibroblasts (CAFs) promote the progression of pancreatic ductal adenocarcinoma (PDAC) via tumor‑stromal interactions. Neutrophil extracellular traps (NETs) are extracellular DNA meshworks released from neutrophils together with proteolytic enzymes against foreign pathogens. Emerging studies suggest their contribution to liver metastasis in several types of cancer. Herein, in order to investigate the role of NETs in liver metastasis in PDAC, the effects of NET inhibitors on spontaneous PDAC mouse models were evaluated. It was demonstrated that DNase I, a NET inhibitor, suppressed liver metastasis. For further investigation, further attention was paid to liver micrometastasis and an experimental liver metastasis mouse model was used that was generated by intrasplenic tumor injection. Furthermore, DNase I also suppressed liver micrometastasis and notably, CAFs accumulated in metastatic foci were significantly decreased in number. In vitro experiments revealed that pancreatic cancer cells induced NET formation and consequently NETs enhanced the migration of hepatic stellate cells, which was the possible origin of CAFs in liver metastasis. On the whole, these results suggest that NETs promote liver micrometastasis in PDAC via the activation of CAFs.
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Copy and paste a formatted citation
Spandidos Publications style
Takesue S, Ohuchida K, Shinkawa T, Otsubo Y, Matsumoto S, Sagara A, Yonenaga A, Ando Y, Kibe S, Nakayama H, Nakayama H, et al: Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. Int J Oncol 56: 596-605, 2020.
APA
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A. ... Nakamura, M. (2020). Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. International Journal of Oncology, 56, 596-605. https://doi.org/10.3892/ijo.2019.4951
MLA
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A., Yonenaga, A., Ando, Y., Kibe, S., Nakayama, H., Iwamoto, C., Shindo, K., Moriyama, T., Nakata, K., Miyasaka, Y., Ohtsuka, T., Toma, H., Tominaga, Y., Mizumoto, K., Hashizume, M., Nakamura, M."Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts". International Journal of Oncology 56.2 (2020): 596-605.
Chicago
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A., Yonenaga, A., Ando, Y., Kibe, S., Nakayama, H., Iwamoto, C., Shindo, K., Moriyama, T., Nakata, K., Miyasaka, Y., Ohtsuka, T., Toma, H., Tominaga, Y., Mizumoto, K., Hashizume, M., Nakamura, M."Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts". International Journal of Oncology 56, no. 2 (2020): 596-605. https://doi.org/10.3892/ijo.2019.4951
Copy and paste a formatted citation
x
Spandidos Publications style
Takesue S, Ohuchida K, Shinkawa T, Otsubo Y, Matsumoto S, Sagara A, Yonenaga A, Ando Y, Kibe S, Nakayama H, Nakayama H, et al: Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. Int J Oncol 56: 596-605, 2020.
APA
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A. ... Nakamura, M. (2020). Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts. International Journal of Oncology, 56, 596-605. https://doi.org/10.3892/ijo.2019.4951
MLA
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A., Yonenaga, A., Ando, Y., Kibe, S., Nakayama, H., Iwamoto, C., Shindo, K., Moriyama, T., Nakata, K., Miyasaka, Y., Ohtsuka, T., Toma, H., Tominaga, Y., Mizumoto, K., Hashizume, M., Nakamura, M."Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts". International Journal of Oncology 56.2 (2020): 596-605.
Chicago
Takesue, S., Ohuchida, K., Shinkawa, T., Otsubo, Y., Matsumoto, S., Sagara, A., Yonenaga, A., Ando, Y., Kibe, S., Nakayama, H., Iwamoto, C., Shindo, K., Moriyama, T., Nakata, K., Miyasaka, Y., Ohtsuka, T., Toma, H., Tominaga, Y., Mizumoto, K., Hashizume, M., Nakamura, M."Neutrophil extracellular traps promote liver micrometastasis in pancreatic ductal adenocarcinoma via the activation of cancer‑associated fibroblasts". International Journal of Oncology 56, no. 2 (2020): 596-605. https://doi.org/10.3892/ijo.2019.4951
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