Side population of a murine mantle cell lymphoma model contains tumour-initiating cells responsible for lymphoma maintenance and dissemination

Francisco Vega, Yogesh Davuluri, Jeong Hee Cho-Vega, Rajesh R. Singh, Shuguang Ma, Rui Yu Wang, Asha S. Multani, Elias Drakos, Lan V. Pham, Yen Chiu Lin Lee, Long Shen, Julian Ambrus, L. Jeffrey Medeiros, Richard J. Ford

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

'Cancer stem cells' or 'tumour initiating cells' in B-cell non-Hodgkin lymphomas have not been demonstrated, although some studies focused on other cancer types suggest that such populations exist and represent tumour cells resistant to therapy and involved in relapse. These cells may also represent a putative neoplastic 'cell of origin' in lymphomas, but there is little substantive data to support this suggestion. Using cell lines derived from a recently established murine IL-14α × c-Myc double transgenic/mantle cell lymphoma-blastoid variant model, heretofore referred to as DTG cell lines, we identified a subset of cells within the side population (SP) with features of 'tumour-initiating cells'. These features include higher expression of ABCG2 and BCL-2, longer telomere length, greater self-renewal ability and higher in vitro clonogenic and in vivo tumorigenic capacities compared with non-SP. In addition, in vitro viability studies demonstrated that the non-SP lymphoma subpopulation has a limited lifespan in comparison with the SP fraction. Syngenic transplant studies showed that non-SP derived tumours, in comparison to the SP-derived tumours, exhibit greater necrosis/apoptosis and less systemic dissemination capability. In conclusion, our data support the interpretation that the DTG SP fraction contains a cell population highly capable of tumour maintenance and systemic dissemination and lends support to the concept that 'tumour-initiating cells' occur in lymphomas.

Original languageEnglish (US)
Pages (from-to)1532-1545
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number6 B
DOIs
StatePublished - Jun 2010
Externally publishedYes

Keywords

  • Cancer stem cells
  • Lymphoma cell lines
  • Side population
  • Tumour initiating cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

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