Freshly isolated bone marrow cells induce death of various carcinoma cell lines

Nicolas Larmonier, François Ghiringhellii, Claire B. Larmonier, Monique Moutet, Annie Fromentin, Emmanuel Baulot, Eric Solary, Bernard Bonnotte, François Martin

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

In some carcinomas such as digestive tract carcinomas, bone marrow infiltration by tumor cells is a frequent event but usually remains a micrometastatic disease and rarely induces overt bone lesions. The mechanisms responsible for the control of these metastases in the bone marrow remain poorly known. We show that freshly isolated bone marrow cells from human, murine and rat origin rapidly kill a wide range of syngeneic or xenogeneic carcinoma cell lines in culture. Further analysis of this cytotoxic process in the rat indicated that neither resident bone marrow macrophages nor NK cells were responsible for this cytotoxic effect that was restricted to a subpopulation of bone marrow cells expressing CD90 (Thy-1), a marker of hemopoietic precursors. The tumoricidal activity of these cells did not require long-term culture nor addition of exogenous cytokines or growth factors. A subset of CD90+ cells that rapidly differentiates into CD163(ED2)-expressing macrophages was observed to be responsible for tumor cell killing. These macrophages induced a non-apoptotic death of tumor cells, a process that required both a direct interaction with the tumor cell and nitric oxide (NO) production through the activation of inducible nitric oxide-synthase (iNOS). This ability of pluripotent hemopoietic stem cells to rapidly differentiate into macrophages capable of killing invasive tumor cells may account for the limited expansion of micrometastases of some carcinomas in the bone marrow.

Original languageEnglish (US)
Pages (from-to)747-756
Number of pages10
JournalInternational Journal of Cancer
Volume107
Issue number5
DOIs
StatePublished - Dec 10 2003

Keywords

  • Bone marrow
  • Carcinoma
  • Cytotoxicity
  • Differentiation
  • Macrophages

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Larmonier, N., Ghiringhellii, F., Larmonier, C. B., Moutet, M., Fromentin, A., Baulot, E., Solary, E., Bonnotte, B., & Martin, F. (2003). Freshly isolated bone marrow cells induce death of various carcinoma cell lines. International Journal of Cancer, 107(5), 747-756. https://doi.org/10.1002/ijc.11463