Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6
Requirements of src family kinase activity associated with CD45 for myeloma cell proliferation by interleukin-6
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DOI：
10.1182/blood.v99.6.2172
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发表时间：
2002-03-15
期刊：
影响因子：
20.3
通讯作者：
Kawano, MM
中科院分区：
文献类型：
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作者：
Ishikawa, H;Tsuyama, N;Kawano, MM
白细胞介素 6 (IL-6) 受体复合物介导的特定细胞内信号，例如信号转导子和转录激活子 3 (STAT 3) 和细胞外信号调节激酶 (ERK) 1/2，被认为负责诱导多种细胞反应。在多发性骨髓瘤中，IL-6仅增强CD45(+)肿瘤细胞的增殖，这些细胞具有不依赖于IL-6的src家族激酶激活，尽管CD45(+)和CD45(-)细胞中STAT3和ERK1/2可以响应IL-6而被激活。此外，Lyn特异性反义寡脱氧核苷酸或选择性src激酶抑制剂显着抑制IL-6诱导的CD45(+) U266骨髓瘤细胞增殖。这些结果表明，STAT3 和 ERK1/2 的激活不足以用于 IL-6 诱导的骨髓瘤细胞系增殖，这些细胞系需要独立于 IL-6 刺激的 src 家族激酶激活。因此，与CD45表达相关的src家族激酶的激活是IL-6使骨髓瘤细胞系增殖的先决条件。我们提出了一种 IL-6 诱导的细胞增殖机制，该机制严格依赖于骨髓瘤的细胞环境。
Specific intracellular signals mediated by interleukin-6 (IL-6) receptor complexes, such as signal transducer and activator of transcription 3 (STAT 3) and extracellular signal-regulated kinase (ERK) 1/2, are considered to be responsible for inducing a variety of cellular responses. In multiple myeloma, IL-6 only enhanced the proliferation of CD45(+) tumor cells that harbored the IL-6-independent activation of src family kinases even though STAT3 and ERK1/2 could be activated in response to IL-6 in both CD45(+) and CD45(-) cells. Furthermore, the IL-6-induced proliferation of CD45(+) U266 myeloma cells was significantly suppressed by Lyn-specific antisense oligodeoxynucleotides or a selective src kinase inhibitor. These results indicate that the activation of both STAT3 and ERK1/2 is not enough for IL-6-induced proliferation of myeloma cell lines that require src family kinase activation independent of IL-6 stimulation. Thus, the activation of the src family kinases associated with CD45 expression is a prerequisite for the proliferation of myeloma cell lines by IL-6. We propose a mechanism for IL-6-induced cell proliferation that is strictly dependent upon the cellular context in myelomas.