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Article

S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer

  • Authors:
    • Hiromichi Nakayama
    • Kenoki Ohuchida
    • Akiko Yonenaga
    • Akiko Sagara
    • Yohei Ando
    • Shin Kibe
    • Shin Takesue
    • Toshiya Abe
    • Sho Endo
    • Kazuhiro Koikawa
    • Takashi Okumura
    • Koji Shido
    • Kei Miyoshi
    • Kohei Nakata
    • Taiki Moriyama
    • Yoshihiro Miyasaka
    • Shigetaka Inoue
    • Takao Ohtsuka
    • Kazuhiro Mizumoto
    • Masafumi Nakamura
  • View Affiliations / Copyright

    Affiliations: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
  • Pages: 211-222
    |
    Published online on: May 24, 2019
       https://doi.org/10.3892/ijo.2019.4812
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Abstract

Lymph node metastasis is an independent prognostic factor in pancreatic cancer. However, the mechanisms of lymph node colonization are unknown. As a mechanism of lymphatic metastasis, it has been reported for other types of cancer that spheroids from tumor cells cause circular chemorepellent‑induced defects (CCIDs) in lymphatic endothelial monolayers. In pancreatic cancer, such mechanisms of metastasis have not been elucidated. The present study evaluated the involvement of this new mechanism of metastasis in pancreatic cancer and investigated the associated factors. In human pancreatic cancer tissue, it was observed that clusters of cancer cells penetrated the wall of lymphatic ducts around the primary tumor. An in vitro co‑culture system was then used to analyze the mechanisms of tumor cell‑mediated disruption of lymphatic vessels. Time‑lapse microscopic imaging revealed that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. CCID formation ability differed depending on the cell line. Neither aggregation of spheroids nor adhesion to lymphatic endothelial cells (LECs) exhibited a significant correlation with this phenomenon. The addition of supernatant from cultured cancer cells enhanced CCID formation. Microarray analysis revealed that the expression of S100 calcium binding protein P (S100P) was significantly increased when LECs were treated with supernatant from cultured cancer cells. Addition of a S100P antagonist significantly suppressed the migration of LECs and CCID formation. The present findings demonstrated that spheroids from pancreatic cancer cells caused circular defects in lymphatic endothelial monolayers. These CCIDs in pancreatic cancer were partly regulated by S100P, suggesting that S100P may be a promising target to inhibit lymph node metastasis.
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Copy and paste a formatted citation
Spandidos Publications style
Nakayama H, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S, Abe T, Endo S, Koikawa K, Koikawa K, et al: S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer. Int J Oncol 55: 211-222, 2019.
APA
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S. ... Nakamura, M. (2019). S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer. International Journal of Oncology, 55, 211-222. https://doi.org/10.3892/ijo.2019.4812
MLA
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S., Takesue, S., Abe, T., Endo, S., Koikawa, K., Okumura, T., Shido, K., Miyoshi, K., Nakata, K., Moriyama, T., Miyasaka, Y., Inoue, S., Ohtsuka, T., Mizumoto, K., Nakamura, M."S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer". International Journal of Oncology 55.1 (2019): 211-222.
Chicago
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S., Takesue, S., Abe, T., Endo, S., Koikawa, K., Okumura, T., Shido, K., Miyoshi, K., Nakata, K., Moriyama, T., Miyasaka, Y., Inoue, S., Ohtsuka, T., Mizumoto, K., Nakamura, M."S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer". International Journal of Oncology 55, no. 1 (2019): 211-222. https://doi.org/10.3892/ijo.2019.4812
Copy and paste a formatted citation
x
Spandidos Publications style
Nakayama H, Ohuchida K, Yonenaga A, Sagara A, Ando Y, Kibe S, Takesue S, Abe T, Endo S, Koikawa K, Koikawa K, et al: S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer. Int J Oncol 55: 211-222, 2019.
APA
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S. ... Nakamura, M. (2019). S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer. International Journal of Oncology, 55, 211-222. https://doi.org/10.3892/ijo.2019.4812
MLA
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S., Takesue, S., Abe, T., Endo, S., Koikawa, K., Okumura, T., Shido, K., Miyoshi, K., Nakata, K., Moriyama, T., Miyasaka, Y., Inoue, S., Ohtsuka, T., Mizumoto, K., Nakamura, M."S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer". International Journal of Oncology 55.1 (2019): 211-222.
Chicago
Nakayama, H., Ohuchida, K., Yonenaga, A., Sagara, A., Ando, Y., Kibe, S., Takesue, S., Abe, T., Endo, S., Koikawa, K., Okumura, T., Shido, K., Miyoshi, K., Nakata, K., Moriyama, T., Miyasaka, Y., Inoue, S., Ohtsuka, T., Mizumoto, K., Nakamura, M."S100P regulates the collective invasion of pancreatic cancer cells into the lymphatic endothelial monolayer". International Journal of Oncology 55, no. 1 (2019): 211-222. https://doi.org/10.3892/ijo.2019.4812
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