Thymidine phosphorylase expressed in macrophages enhances antitumor effect of 5′-deoxy-5-fluorouridine on human colorectal carcinoma cells

Jimin Zhang, Takayuki Mizoi, Nobuhiko Harada, Ken Ichi Shiiba, Kikuo Miyagawa, Seiki Matsuno, Iwao Sasaki

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background: Thymidine phosphorylase (dThdPase) is a key enzyme in the activation of the pro-drugs of 5-fluorouracil (5-FU), 5′-deoxy-5-fluoroufidine (5′-DFUR) and capecitabine. In colorectal carcinoma (CRC), the major cells expressing dThdPase have been shown to be stromal cells, particularly macrophages. Materials and Methods: The present study was designed to clarify whether dThdPase expressed in macrophage-like cell lines, THP-1 and U937, and monocyte-rich mononuclear cells (MoMNCs) from human peripheral blood can modulate the antitumor effect of 5′-DFUR on CRC cells. Results: dThdPase protein was found in THP-1 and U937 by ELISA, while little or no dThdPase could be detected in the CRC cell lines tested. Incubation of 5′-DFUR with the macrophage-like cells significantly enhanced the antitumor effect of 5′-DFUR in a 5-DFUR sensitivity assay compared with untreated 5′-DFUR. MoMNCs also showed a similar effect. When the media containing 5′-DFUR was treated with either THP-1 or U937 cells, detectable levels of 5-FU could be measured in the treated media. Conclusion: These data suggest that macrophages convert 5′-DFUR to 5-FU and release the converted 5-FU, resulting in an enhancement of the antitumor effect of 5′-DFUR.

Original languageEnglish
Pages (from-to)323-329
Number of pages7
JournalAnticancer research
Volume23
Issue number1 A
Publication statusPublished - 2003 Jan
Externally publishedYes

Keywords

  • 5′-deoxy-5-fluorouridine
  • Colorectal carcinoma
  • Macrophage
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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