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Hodgkin's disease derived cell lines: a review
1Fujisaki Cell Center, Hayashibara Biochemical Labs., Inc.
Insights
Eight Hodgkin
Area of Science:
- Hematology and Oncology
- Cell Biology
- Immunology
Background:
- Hodgkin lymphoma (HL) cell lines are crucial for studying the disease's pathogenesis.
- Previous studies have established numerous HL cell lines, but their true representation of in vivo Hodgkin Reed-Sternberg (H-RS) cells is debated.
- Understanding the cellular origin and lineage of H-RS cells remains a key challenge in HL research.
Purpose of the Study:
- To evaluate and characterize established Hodgkin lymphoma (HL) cell lines.
- To determine the lineage and differentiation state of these HL cell lines.
- To compare the in vitro characteristics of HL cell lines with in vivo H-RS cells.
Main Methods:
- Analysis of 15 established cell lines using immunostaining and molecular genetic data.
- Assessment of surface marker expression, including T- and B-cell antigens and unique activation markers.
- Review of existing data on cytokine production, chromosomal abnormalities, and proto-oncogene expression.
Main Results:
- Eight of the 15 studied cell lines (CO, DEV, HD-70, HDLM, KM-H2, L-428, L-540, SUP-HD1) were identified as true Hodgkin lymphoma cell lines.
- These cell lines were assigned to either T-cell (CO, HDLM, L-540) or B-cell (DEV, HD-70, KM-H2, SUP-HD1) lineages, with L-428 showing a probable lymphoid origin.
- All eight cell lines, predominantly from the nodular sclerosis subtype, share expression of key markers (CD15, CD25, CD30, CD71, HLA-DR) with in vivo H-RS cells.
Conclusions:
- Established Hodgkin lymphoma cell lines exhibit phenotypical similarities to in vivo H-RS cells, suggesting a lymphoid origin.
- The findings are primarily applicable to the nodular sclerosis subtype of Hodgkin lymphoma.
- Further research is warranted to clarify the differentiation state and potential non-lymphoid origins of H-RS cells.
Abstract:
A number of so-called "HD cell lines" have been established over the last 10-15 years (Table 1). Or those 15 cell lines we studied, only the cell lines CO, DEV, HD-70, HDLM, KM-H2, L-428, L-540 and SUP-HD1 can be regarded to represent true HD cell lines. According to the immunostaining results and molecular genetic data, these 8 cell lines can be assigned either to the T-cell lineage (CO, HDLM, L-540) or B-cell lineage (DEV, HD-70, KM-H2, SUP-HD1). With the data currently available, the cell lineage origin of L-428 cannot be unequivocally determined, but appears to be lymphoid. All but one of these eight HD cell lines have been established from patients with the nodular sclerosis subtype. Therefore, the conclusions drawn from the in vitro studies are limited to this histological subtype of HD. It is conceivable that culture conditions select for a particular type of cell that will survive. The state of differentiation of these HD cell lines remains unclear due to the incomplete expression of T- or B-cell antigens. The in vitro cells and the in vivo H-RS cells share, however, the expression of the unique activation markers CD15, CD25, CD30, CD71 and HLA-DR. Recently published data indicate that the HD cell lines express and produce a large number of cytokines. Multiple non-random chromosomal abnormalities and the expression of various proto-oncogenes are also new and exciting findings and certainly deserve further study. In summary, although the cultured cells are not unequivocally proven to be the direct progeny of in vivo H-RS cells, several continuous HD cell lines have been established that display a variety of phenotypical features identical or similar to those of their presumed in vivo counterparts. Surface marker, molecular genetic and other features suggest a T- or B-cell derivation. An extrapolation of these conclusions would point to a lymphoid origin of H-RS cells. Whether H-RS cells can originate from other cell types such as monocytes/macrophages or reticulum cells, cannot be answered with the currently available HD cell lines.