Live imaging of tumor initiation in zebrafish larvae reveals a trophic role for leukocyte-derived PGE₂

Yi Feng, Stephen Renshaw, Paul Martin

Research output: Contribution to journalArticlepeer-review

Abstract

Epidemiology studies and clinical trials have suggested that the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, can significantly reduce the incidence of and mortality associated with many cancers, and upregulation of the COX2-PGE(2) pathway in tumor microenvironments might drive several aspects of cancer progression. For these reasons, the mechanisms linking COX blockade and cancer prevention have long been an area of active investigation. During carcinogenesis, COX-2 is expressed both by malignant epithelial cells and by tumor-associated stromal cells, including macrophages, but the observation that NSAIDs are most effective in cancer prevention in APC(min/+) mice if the mice are treated from conception suggests that the COX-2/PGE(2) pathway might also be critical at the earliest stages of tumor development. In this study we take advantage of the translucency and genetic tractability of zebrafish larvae to investigate the involvement of inflammatory cells at cancer initiation, when transformed cells first arise in tissues. We previously showed that innate immune cells supply early transformed cells with proliferative cues and, by using complementary pharmacological and genetic experiments, we now show that prostaglandin E(2) (PGE(2)) is the trophic signal required for this expansion of transformed cells. Our in vivo observations at these early stages of cancer initiation provide a potential mechanistic explanation for why long-term use of low doses of NSAIDs, including aspirin, might reduce cancer onset.
Original languageEnglish
Pages (from-to)1253-9
Number of pages7
JournalCurrent biology : CB
Volume22
Issue number13
DOIs
Publication statusPublished - 10 Jul 2012

Keywords

  • Animals
  • Animals, Genetically Modified
  • Cell Death
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Dinoprostone
  • Disease Models, Animal
  • Larva
  • Leukocytes
  • Macrophages
  • Neutrophils
  • Proto-Oncogene Proteins p21(ras)
  • Receptors, Prostaglandin E, EP1 Subtype
  • Zebrafish

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