Open AccessSide population of a murine mantle cell lymphoma model contains tumour‐initiating cells responsible for lymphoma maintenance and dissemination
Author(s) -
Vega Francisco,
Davuluri Yogesh,
ChoVega Jeong Hee,
Singh Rajesh R.,
Ma Shuguang,
Wang RuiYu,
Multani Asha S.,
Drakos Elias,
Pham Lan V.,
Lee YenChiu Lin,
Shen Long,
Ambrus Jr Julian,
Medeiros L. Jeffrey,
Ford Richard J.
Publication year - 2010
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2009.00865.x
Subject(s) - mantle cell lymphoma , clonogenic assay , biology , cancer research , lymphoma , side population , population , syngenic , cancer cell , stem cell , cancer stem cell , cell culture , cancer , immunology , medicine , microbiology and biotechnology , genetics , immune system , environmental health
‘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.