Mast cells are an essential hematopoietic component for polyp development

Elias Gounaris, Susan E. Erdman, Clifford Restaino, Michael F. Gurish, Daniel S. Friend, Fotini Gounari, David M. Lee, Guoying Zhang, Jonathan N. Glickman, Kichul Shin, Varada P. Rao, Theofilos Poutahidis, Ralph Weissleder, Kelly M. McNagny, Khashayarsha Khazaie

Research output: Contribution to journalArticle

189 Scopus citations

Abstract

It is generally agreed that most colon cancers develop from adenomatous polyps, and it is this fact on which screening strategies are based. Although there is overwhelming evidence to link intrinsic genetic lesions with the formation of these preneoplastic lesions, recent data suggest that the tumor stromal environment also plays an essential role in this disease. In particular, it has been suggested that CD34+ immature myeloid precursor cells are required for tumor development and invasion. Here we have used mice conditional for the stabilization of β-catenin or defective for the adenomatous polyposis coli (APC) gene to reinvestigated the identity and importance of tumor-infiltrating hematopoietic cells in polyposis. We show that, from the onset, polyps are infiltrated with proinflammatory mast cells (MC) and their precursors. Depletion of MC either pharmacologically or through the generation of chimeric mice with genetic lesions in MC development leads to a profound remission of existing polyps. Our data suggest that MC are an essential hematopoietic component for preneoplastic polyp development and are a novel target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)19977-19982
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number50
DOIs
StatePublished - Dec 11 2007

Keywords

  • Cancer
  • Inflammation
  • Polyposis
  • TNFα

ASJC Scopus subject areas

  • General

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    Gounaris, E., Erdman, S. E., Restaino, C., Gurish, M. F., Friend, D. S., Gounari, F., Lee, D. M., Zhang, G., Glickman, J. N., Shin, K., Rao, V. P., Poutahidis, T., Weissleder, R., McNagny, K. M., & Khazaie, K. (2007). Mast cells are an essential hematopoietic component for polyp development. Proceedings of the National Academy of Sciences of the United States of America, 104(50), 19977-19982. https://doi.org/10.1073/pnas.0704620104