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Biomed Res Int. 2014;2014:510408.

Establishment of cell lines from both myeloma bone marrow and plasmacytoma: SNU_MM1393_BM and SNU_MM1393_SC from a single patient.

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제1저자 고영일 · 교신저자 윤성수

PMID 25343143 PMC4197890 DOI 10.1155/2014/510408 IF 2.9 혈액종양내과
소속 (4)
  1. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-Ku, Seoul 110-744, Republic of Korea.
  2. Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-Ku, Seoul 110-799, Republic of Korea.
  3. Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-Ku, Seoul 110-799, Republic of Korea ; Functional Genome Institute, PDXen Biosystem Inc., 437 Dongil-ro, Kwangjin-Ku, Seoul 143-901, Republic of Korea.
  4. Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-Ku, Seoul 110-744, Republic of Korea ; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-Ku, Seoul 110-799, Republic of Korea.

Abstract

PURPOSE We tried to establish clinically relevant human myeloma cell lines that can contribute to the understanding of multiple myeloma (MM).

MATERIALS AND METHODS Mononuclear cells obtained from MM patient's bone marrow were injected via tail vein in an NRG/SCID mouse. Fourteen weeks after the injection, tumor developed at subcutis of the mouse. The engraftment of MM cells into mouse bone marrow (BM) was also observed. We separated and cultured cells from subcutis and BM.

RESULTS After the separation and culture of cells from subcutis and BM, we established two cell lines originating from a single patient (SNU_MM1393_BM and SNU_MM1393_SC). Karyotype of the two newly established MM cell lines showed tetraploidy which is different from the karyotype of the patient (diploidy) indicating clonal evolution. In contrast to SNU_MM1393_BM, cell proliferation of SNU_MM1393_SC was IL-6 independent. SNU_MM1393_BM and SNU_MM1393_SC showed high degree of resistance against bortezomib compared to U266 cell line. SNU_MM1393_BM had the greater lethality compared to SNU_MM1393_SC.

CONCLUSION Two cell lines harboring different site tropisms established from a single patient showed differences in cytokine response and lethality. Our newly established cell lines could be used as a tool to understand the biology of multiple myeloma.

Figures

Figure 1
Figure 1 Representative appearances of histopathologic hematoxylin and eosin (H&E) staining of the irradiated bone marrow (a), bone marrow of the leg with cancer cell infiltration (b), and tumors at subcutis (c).
Figure 2
Figure 2 Karyotype of SNU_MM1393_BM (a) and SNU_MM1393_SC (b) cell line using G-banding.
Figure 3
Figure 3 Flow cytometry analysis of SNU_MM1393_BM and SNU_MM1393_SC cell lines. Expression of CD138 and CD45 of both cell lines was analyzed using fluorescein-activated cell sorting (FACS).
Figure 4
Figure 4 Western blot showing response to IL-6 in SNU_MM1393_BM and SNU_MM1393_SC. Whole cell lysates obtained from both cell lines were treated with IL-6, sIL-6R, and combined IL-6 and sIL-6R for 30 min (1: control, 2: IL-6 5 ng/mL, 3: sIL-6R 25 ng/mL, and 4: IL-6 5 ng/mL + sIL-6R 25 ng/mL).
Figure 5
Figure 5 Production of IL-6 from SNU_MM1393_BM and SNU_MM1393_SC, U266, RPMI8226, and IM9.
Figure 6
Figure 6 Growth inhibitory effect of bortezomib (a), panobinostat (b), and combination of bortezomib and panobinostat (c) in newly established MM cell lines. The data shows the mean ± standard error of three independent experiments.

그림 출처: PubMed Central 공개 논문 (PMC4197890)

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
BioMed research international · eISSN 2314-6141
전자 출판
2014-08-12
MeSH
Animals · Bone Marrow / pathology · Cell Culture Techniques / methods · Cell Differentiation · Cell Line · Humans · Male · Mice · Middle Aged · Multiple Myeloma / pathology · Plasmacytoma / pathology
참고문헌
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