Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1997-2-24
|
| pubmed:abstractText |
Although IL-6 has been identified as a major growth factor in multiple myeloma (MM), it is believed that maintenance of tumor growth in vivo depends on one or more additional stroma-derived factors. We describe a new human myeloma cell line (MM5.1) that can be maintained in the presence of bone marrow-derived stromal cell layers, and not only when cultured with exogeneous IL-6. This cell line expresses the same immunoglobulin kappa light chain RNA sequence as the patient's original tumor cells, has a plasma cell morphology and expresses plasma cell antigens (cytoplasmic kappa light chain, CD38, BB4). Without the presence of stromal factors, MM5.1 cells become apoptotic. A low proliferative effect was observed in the presence of oncostatin M (OSM) but other cytokines (IL-10, IL-11, stem cell factor (SCF) and leukemia inhibitory factor (LIF)) had no effect at all. We observed that MM5.1 cells also grow when physically separated from stromal cell layers by a 0.45 microm microporous membrane or when cultured in conditioned medium from stromal marrow cells. Unexpectedly, the growth in stromal supernatants was markedly inhibited by an anti-IL-6 antiserum and an anti-IL-6 receptor transducer chain (gp130) mAb in a dose-dependent manner. This implies that MM5.1 cells are IL-6 responsive only when exposed to one or more additional soluble factor(s) derived from bone marrow stroma. Coculturing MM5.1 cells with IL-6 and cytokines that were described to increase the IL-6 responsiveness of myeloma cells (G-CSF, GM-CSF and IL-3) had no effect on the growth or survival. A strong proliferative effect was observed when MM5.1 cells were cultured with IL-6 and soluble IL-6 receptor (sgp80). However no sgp80 could be detected in stromal supernatants using a sensitive immunoassay. This indicates that sustained proliferation of the MM5.1 cell line depends on a combination of IL6 and at least one, thus far unidentified, stroma-derived factor. After more than 1 year in continuous culture, we could obtain a variant of the line (MM5.2) that shows an improved growth rate and grows stroma independently. Molecular analysis revealed clonal identity with the early passage form and Epstein-Barr virus antigen expression was negative. The two variants of this cell line offer a useful model to identify molecular mechanisms involved in clonal evolution towards stroma-independent growth of myeloma cells.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloma Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-6
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0887-6924
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
11
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
284-93
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9009094-Adipose Tissue,
pubmed-meshheading:9009094-Antigens, CD,
pubmed-meshheading:9009094-Antigens, Neoplasm,
pubmed-meshheading:9009094-Apoptosis,
pubmed-meshheading:9009094-Bone Marrow,
pubmed-meshheading:9009094-Bone Marrow Cells,
pubmed-meshheading:9009094-Coculture Techniques,
pubmed-meshheading:9009094-Connective Tissue,
pubmed-meshheading:9009094-Culture Media, Conditioned,
pubmed-meshheading:9009094-Disease Progression,
pubmed-meshheading:9009094-Humans,
pubmed-meshheading:9009094-Immunophenotyping,
pubmed-meshheading:9009094-Interleukin-6,
pubmed-meshheading:9009094-Male,
pubmed-meshheading:9009094-Middle Aged,
pubmed-meshheading:9009094-Multiple Myeloma,
pubmed-meshheading:9009094-Myeloma Proteins,
pubmed-meshheading:9009094-Receptors, Interleukin,
pubmed-meshheading:9009094-Receptors, Interleukin-6,
pubmed-meshheading:9009094-Selection, Genetic,
pubmed-meshheading:9009094-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Establishment and characterization of a human stroma-dependent myeloma cell line (MM5.1) and its stroma-independent variant (MM5.2).
|
| pubmed:affiliation |
Department Hematology-Immunology, Free University Brussels, Belgium.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|