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Leukemia ; 16(10): 2142-7, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12357369

ABSTRACT

Interleukin 6 (IL-6) is known to play an important role in the biology of the malignant plasma cells in multiple myeloma. In an effort to better understand IL-6 stimulated myeloma cell growth, we have performed gene expression profiling to identify IL-6 early response genes. Using the KAS-6/1 IL-6-dependent human myeloma cell line, IL-6 stimulation dramatically induced expression of monocyte chemoattractant protein-1 (MCP-1) mRNA. To verify this result, we used reverse transcriptase PCR and RNAse protection assays and demonstrated using both assays that MCP-1 is indeed an IL-6 responsive gene in a variety of IL-6-responsive myeloma cell lines. Moreover, we also demonstrated IL-6 stimulated MCP-1 secretion by the myeloma cell lines as well as by fresh patient tumor cells. Lastly, we present evidence that fresh patient tumor cells express mRNA for the MCP-1 receptor, CCR2, as do myeloma cell lines along with a second MCP-1 receptor, CCR11. Although MM cell chemotaxis in response to MCP-1 was only minimal, we were able to demonstrate that MCP-1 stimulated activation of MAPK. Because of the important role that this chemokine plays in both angiogenesis and bone homeostasis, and the ability of MCP-1 to activate myeloma cells, these results suggest a new mechanism by which IL-6 may contribute to disease pathogenesis.


Subject(s)
Chemokine CCL2/genetics , Interleukin-6/physiology , Multiple Myeloma/metabolism , Base Sequence , DNA Primers , DNA, Complementary , Enzyme Activation , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Mitogen-Activated Protein Kinases/metabolism , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , Tumor Cells, Cultured
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