Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

Evgeniya V. DolgovaEmail author View ORCID ID profile,
Daria D. Petrova,
Anastasia S. Proskurina,
Genrikh S. Ritter,
Polina E. Kisaretova,
Ekaterina A. Potter,
Yaroslav R. Efremov,
Sergey I. Bayborodin,
Tatiana V. Karamysheva,
Margarita V. Romanenko,
Sergey V. Netesov,
Oleg S. Taranov,
Aleksandr A. Ostanin,
Elena R. Chernykh and
Sergey S. Bogachev

Cancer Cell International201919:120

https://doi.org/10.1186/s12935-019-0842-x

Received: 12 February 2019
Accepted: 27 April 2019
Published: 6 May 2019

Abstract

Background

We have characterized the human cell line arised from the Epstein–Barr virus (EBV) positive multiple myeloma aspirate subjected to the long-term cultivation. This cell line has acquired the ability to form free-floating spheres and to produce a xenograft upon transplantation into NOD/SCID mice.

Methods

Cells from both in vitro culture and developed xenografts were investigated with a number of analytical approaches, including pathomorphological analysis, FISH analysis, and analysis of the surface antigens and of the VDJ locus rearrangement.

Results

The obtained results, as well as the confirmed presence of EBV, testify that both biological systems are derived from B-cells, which, in turn, is a progeny of the EBV-transformed B-cellular clone that supplanted the primordial multiple myeloma cells. Next we assessed whether cells that (i) were constantly present in vitro in the investigated cell line, (ii) were among the sphere-forming cells, and (iii) were capable of internalizing a fluorescent TAMRA-labeled DNA probe (TAMRA+ cells) belonged to one of the three types of undifferentiated bone marrow cells of a multiple myeloma patient: CD34+ hematopoietic stem cells, CD90+ mesenchymal stem cells, and clonotypic multiple myeloma cell.

Conclusion

TAMRA+ cells were shown to constitute the fourth independent subpopulation of undifferentiated bone marrow cells of the multiple myeloma patient. We have demonstrated the formation of ectopic contacts between TAMRA+ cells and cells of other types in culture, in particular with CD90+ mesenchymal stem cells, followed by the transfer of some TAMRA+ cell material into the contacted cell.