Chronic inflammation-derived nitric oxide causes conversion of human colonic adenoma cells into adenocarcinoma cells

Hiroshi Tazawa, Tokuichi Kawaguchi, Tokushige Kobayashi, Yasuhiro Kuramitsu, Sayori Wada, Yoshiko Satomi, Hoyoku Nishino, Masanobu Kobayashi, Yusuke Kanda, Mitsuhiko Osaki, Tomoyuki Kitagawa, Masuo Hosokawa, Futoshi Okada

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

It has been suggested that nitric oxide (NO) derived from chronically inflamed tissues is a cause of carcinogenesis. We herein demonstrated that administration of an inducible NO synthase inhibitor, aminoguanidine, significantly suppressed the tumorigenic conversion of human colonic adenoma (FPCK-1-1) cells into adenocarcinoma (FPCK/Inflam) cells accelerated by foreign body-induced chronic inflammation in nude mice. To determine whether NO directly promotes carcinogenesis, we exposed FPCK-1-1 cells continuously to chemically generated NO (FPCK/NO), and periodically examined their tumorigenicity. FPCK/NO cells formed tumors, whereas vehicle-treated cells (FPCK/NaOH) did not. We selected a tumorigenic population from FPCK/NO cells kept it in three-dimensional (3D) culture where in vivo-like multicellular spheroidal growth was expected. FPCK/Inflam cells developed large spheroids whereas FPCK/NO cells formed tiny but growing compact aggregates in 3D culture. Meanwhile, FPCK-1-1 and FPCK/NaOH cells underwent anoikis (apoptotic cell death consequential on insufficient cell-to-substrate interactions) through activation of caspase 3. The survived cells in the 3D culture (FPCK/NO/3D), which were derived from FPCK/NO cells, showed a similar tumor incidence to that of FPCK/Inflam cells. These results showed that NO was one of the causative factors for the acceleration of colon carcinogenesis, especially in the conversion from adenoma to adenocarcinoma in the chronic inflammatory environment.

Original languageEnglish
Pages (from-to)2835-2844
Number of pages10
JournalExperimental Cell Research
Volume319
Issue number18
DOIs
Publication statusPublished - Nov 1 2013

Keywords

  • Anoikis
  • Chronic inflammation
  • Colon carcinogenesis
  • Human colonic adenoma cells
  • Nitric oxide
  • Three-dimensional culture

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Tazawa, H., Kawaguchi, T., Kobayashi, T., Kuramitsu, Y., Wada, S., Satomi, Y., Nishino, H., Kobayashi, M., Kanda, Y., Osaki, M., Kitagawa, T., Hosokawa, M., & Okada, F. (2013). Chronic inflammation-derived nitric oxide causes conversion of human colonic adenoma cells into adenocarcinoma cells. Experimental Cell Research, 319(18), 2835-2844. https://doi.org/10.1016/j.yexcr.2013.08.006