Induction of cyclooxygenase-2 in monocyte/macrophage by mucins secreted from colon cancer cells Academic Article uri icon

Overview

MeSH Major

  • Colonic Neoplasms
  • Isoenzymes
  • Macrophages
  • Monocytes
  • Mucins
  • Prostaglandin-Endoperoxide Synthases

abstract

  • Up-regulation of cyclooxygenase-2 (COX-2) and overproduction of prostaglandins have been implicated in the initiation and/or progression of colon cancer. However, it is uncertain in which cells and how COX-2 is induced initially in the tumor microenvironment. We found that a conditioned medium of the colon cancer cell line, LS 180, contained a factor to induce COX-2 in human peripheral blood mononuclear cells. This factor was purified biochemically and revealed to be mucins. A small amount of mucins (approximately 100 ng of protein per ml) could elevate prostaglandin E2 production by monocytes. The mucins induced COX-2 mRNA and protein levels of monocytes in a dose- and time-dependent manner, indicating a COX-2-mediated pathway. We also have examined immunohistochemically the localization of COX-2 protein and mucins in human colorectal cancer tissues. It is noteworthy that COX-2-expressing macrophages were located around the region in which mucins were detectable, suggesting that COX-2 also was induced by mucins in vivo. These results suggest that mucins produced by colon cancer cells play a critical role in the initial induction of COX-2 in the tumor microenvironment.

publication date

  • March 4, 2003

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC151410

Digital Object Identifier (DOI)

  • 10.1073/pnas.0435410100

PubMed ID

  • 12598658

Additional Document Info

start page

  • 2736

end page

  • 41

volume

  • 100

number

  • 5