Skip to main content
Erschienen in: International Journal of Hematology 4/2010

01.11.2010 | Original Article

Establishment of an HS23 stromal cell-dependent myeloma cell line: fibronectin and IL-6 are critical

verfasst von: Akira Sakai, Miyo Oda, Mitsuhiro Itagaki, Noriaki Yoshida, Koji Arihiro, Akiro Kimura

Erschienen in: International Journal of Hematology | Ausgabe 4/2010

Einloggen, um Zugang zu erhalten

Abstract

A multiple myeloma (MM) cell line, MSG1, which depends on HS23 stromal cells for its survival, was established from the pleural effusion of a patient with MM who expressed the M-protein of IgA-λ in his serum. During the first 2 months of culture, the myeloma cells survived on adhesive cells from the pleural effusion and, subsequently, they continued to proliferate on HS23 stromal cells. The phenotype of the established MSG1 cell line was: CD138+, CD38++, CD19, CD56, VLA-4+, VEGFR1+ and VEGFR2+. Immunohistochemical staining also demonstrated expression of the IgA and λ chain in MSG1 cytoplasm. Karyotype analysis indicated complex chromosomal abnormalities; hypertriploidy, including the deletion of chromosomes 13 and 17, and c-myc translocation. MSG1 cells continued to proliferate, not only when co-cultured with HS23 cells, but also when cultured only on fibronectin-coated plates with the supernatant of HS23 cells or with control medium containing IL-6. Tocilizumab, an anti-IL-6 receptor antibody, inhibited MSG1 survival under these conditions. Therefore, MSG1 may be a unique myeloma cell line that is useful for the study of cell adhesion-mediated drug resistance induced by adhesion molecules and IL-6 stimulation of myeloma cells.
Literatur
1.
Zurück zum Zitat Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Can. 2007;7:585–97.CrossRef Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Can. 2007;7:585–97.CrossRef
2.
Zurück zum Zitat Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93:1658–67.PubMed Damiano JS, Cress AE, Hazlehurst LA, Shtil AA, Dalton WS. Cell adhesion mediated drug resistance (CAM-DR): role of integrins and resistance to apoptosis in human myeloma cell lines. Blood. 1999;93:1658–67.PubMed
3.
Zurück zum Zitat Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T, et al. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood. 2004;104:2484–91.CrossRefPubMed Abe M, Hiura K, Wilde J, Shioyasono A, Moriyama K, Hashimoto T, et al. Osteoclasts enhance myeloma cell growth and survival via cell-cell contact: a vicious cycle between bone destruction and myeloma expansion. Blood. 2004;104:2484–91.CrossRefPubMed
4.
Zurück zum Zitat Sakai A, Marti GE, Caporaso N, Pittaluga S, Touchman JW, Fend F, et al. Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL. Blood. 2000;95:1413–9.PubMed Sakai A, Marti GE, Caporaso N, Pittaluga S, Touchman JW, Fend F, et al. Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL. Blood. 2000;95:1413–9.PubMed
5.
Zurück zum Zitat Roecklein BA, Torok-Storb B. Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. Blood. 1995;85:997–1005.PubMed Roecklein BA, Torok-Storb B. Functionally distinct human marrow stromal cell lines immortalized by transduction with the human papilloma virus E6/E7 genes. Blood. 1995;85:997–1005.PubMed
6.
Zurück zum Zitat Maniatis T, Fritsch E, Sambrook I. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory. 1987. Maniatis T, Fritsch E, Sambrook I. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory. 1987.
7.
Zurück zum Zitat Shibata D, Weiss LM, Nathwani BN, Brynes RK, Levine AM. Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin’s lymphoma. Blood. 1991;77:1527–33.PubMed Shibata D, Weiss LM, Nathwani BN, Brynes RK, Levine AM. Epstein-Barr virus in benign lymph node biopsies from individuals infected with the human immunodeficiency virus is associated with concurrent or subsequent development of non-Hodgkin’s lymphoma. Blood. 1991;77:1527–33.PubMed
8.
Zurück zum Zitat Monini P, Lellis LD, Fabris M, Rigolin F, Cassai E. Kaposi’s sarcoma-associated herpesvirus DNA sequences in prostate tissue and human semen. New Eng J Med. 1996;334:1168–72.CrossRefPubMed Monini P, Lellis LD, Fabris M, Rigolin F, Cassai E. Kaposi’s sarcoma-associated herpesvirus DNA sequences in prostate tissue and human semen. New Eng J Med. 1996;334:1168–72.CrossRefPubMed
9.
Zurück zum Zitat Kawano MM, Hunag N, Harada H, Harada Y, Sakai A, Tanaka H, et al. Identification of immature and mature myeloma cells in the bone marrow of human myelomas. Blood. 1993;82:564–70.PubMed Kawano MM, Hunag N, Harada H, Harada Y, Sakai A, Tanaka H, et al. Identification of immature and mature myeloma cells in the bone marrow of human myelomas. Blood. 1993;82:564–70.PubMed
10.
Zurück zum Zitat Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998;91:3–21.PubMed Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood. 1998;91:3–21.PubMed
11.
Zurück zum Zitat Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T, et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood. 2001;98:428–35.CrossRefPubMed Podar K, Tai YT, Davies FE, Lentzsch S, Sattler M, Hideshima T, et al. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood. 2001;98:428–35.CrossRefPubMed
12.
Zurück zum Zitat Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332:83–5.CrossRefPubMed Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature. 1988;332:83–5.CrossRefPubMed
13.
Zurück zum Zitat Di Raimondo F, Azzaro MP, Palumbo G, Bagnato S, Giustolisi G, Floridia P, et al. Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. Haematologica. 2000;85:800–5.PubMed Di Raimondo F, Azzaro MP, Palumbo G, Bagnato S, Giustolisi G, Floridia P, et al. Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. Haematologica. 2000;85:800–5.PubMed
14.
Zurück zum Zitat Dankbar B, Padro T, Leo R, Feldmann B, Kropff K, Mesters RM, et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood. 2000;95:2630–6.PubMed Dankbar B, Padro T, Leo R, Feldmann B, Kropff K, Mesters RM, et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood. 2000;95:2630–6.PubMed
15.
Zurück zum Zitat Ramakrishnan V, Timm M, Haug JL, Kimlinger TK, Wellik LE, Witzig TE, et al. Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs. Oncogene. 2010;29:1190–202.CrossRefPubMed Ramakrishnan V, Timm M, Haug JL, Kimlinger TK, Wellik LE, Witzig TE, et al. Sorafenib, a dual Raf kinase/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs. Oncogene. 2010;29:1190–202.CrossRefPubMed
16.
Zurück zum Zitat Yoshino-Hoshino N, Adachi Y, Aoki C, Pereboev A, Curiel DT, Nishimoto N. Establishment of a new interleukin-6 (IL-6) receptor inhibitor applicable to the gene therapy for IL-6-dependent tumor. Cancer Res. 2007;67:871–975.CrossRef Yoshino-Hoshino N, Adachi Y, Aoki C, Pereboev A, Curiel DT, Nishimoto N. Establishment of a new interleukin-6 (IL-6) receptor inhibitor applicable to the gene therapy for IL-6-dependent tumor. Cancer Res. 2007;67:871–975.CrossRef
17.
Zurück zum Zitat Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, et al. Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 2009;28:231–42.CrossRefPubMed Noborio-Hatano K, Kikuchi J, Takatoku M, Shimizu R, Wada T, Ueda M, et al. Bortezomib overcomes cell adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 2009;28:231–42.CrossRefPubMed
18.
Zurück zum Zitat Matsuo Y, Drexler HG, Nishizaki C, Harashima A, Fukuda S, Kozuka T, et al. Human bone marrow stroma-dependent cell line MOLP-5 derived from a patient in leukaemic phase of multiple myeloma. Br J Haemat. 2000;109:54–63.CrossRef Matsuo Y, Drexler HG, Nishizaki C, Harashima A, Fukuda S, Kozuka T, et al. Human bone marrow stroma-dependent cell line MOLP-5 derived from a patient in leukaemic phase of multiple myeloma. Br J Haemat. 2000;109:54–63.CrossRef
Metadaten
Titel
Establishment of an HS23 stromal cell-dependent myeloma cell line: fibronectin and IL-6 are critical
verfasst von
Akira Sakai
Miyo Oda
Mitsuhiro Itagaki
Noriaki Yoshida
Koji Arihiro
Akiro Kimura
Publikationsdatum
01.11.2010
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 4/2010
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-010-0698-2

Weitere Artikel der Ausgabe 4/2010

International Journal of Hematology 4/2010 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.