Universität zu Köln

Rengstl, Benjamin, Kim, Sooji, Doering, Claudia, Weiser, Christian, Bein, Julia, Bankov, Katrin, Herling, Marco, Newrzela, Sebastian, Hansmann, Martin-Leo and Hartmann, Sylvia (2017). Small and big Hodgkin-Reed-Sternberg cells of Hodgkin lymphoma cell lines L-428 and L-1236 lack consistent differences in gene expression profiles and are capable to reconstitute each other. PLoS One, 12 (5). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

The hallmark of classical Hodgkin lymphoma (cHL) is the presence of giant, mostly multinucleated Hodgkin-Reed-Sternberg (HRS) cells. Whereas it has recently been shown that giant HRS cells evolve from small Hodgkin cells by incomplete cytokinesis and re-fusion of tethered sister cells, it remains unsolved why this phenomenon particularly takes place in this lymphoma and what the differences between these cell types of variable sizes are. The aim of the present study was to characterize microdissected small and giant HRS cells by gene expression profiling and to assess differences of clonal growth behavior as well as susceptibility toward cytotoxic intervention between these different cell types to provide more insight into their distinct cellular potential. Applying stringent filter criteria, only two differentially expressed genes between small and giant HRS cells, SHFM1 and LDHB, were identified. With looser filter criteria, 13 genes were identified to be differentially overexpressed in small compared to giant HRS cells. These were mainly related to energy metabolism and protein synthesis, further suggesting that small Hodgkin cells resemble the proliferative compartment of cHL. SHFM1, which is known to be involved in the generation of giant cells, was downregulated in giant RS cells at the RNA level. However, reduced mRNA levels of SHFM1, LDHB and HSPA8 did not translate into decreased protein levels in giant HRS cells. In cell culture experiments it was observed that the fraction of small and big HRS cells was adjusted to the basic level several days after enrichment of these populations via cell sorting, indicating that small and big HRS cells can reconstitute the full spectrum of cells usually observed in the culture. However, assessment of clonal growth of HRS cells indicated a significantly reduced potential of big HRS cells to form single cell colonies. Taken together, our findings pinpoint to strong similarities but also some differences between small and big HRS cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rengstl, Benjamin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kim, Sooji UNSPECIFIED UNSPECIFIED UNSPECIFIED Doering, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiser, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Bein, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Bankov, Katrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Newrzela, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hansmann, Martin-Leo UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-231131
DOI:	10.1371/journal.pone.0177378
Journal or Publication Title:	PLoS One
Volume:	12
Number:	5
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CANCER STEM-CELLS; SIDE-POPULATION; PROTEIN BRCA2; B-CELLS; DISEASE; CYTOKINESIS; LYMPHOCYTES; IDENTIFICATION; TARGET; KM-H2 Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23113