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The interleukin-6 (IL-6) signal is transduced through membrane-anchored gp130, which is associated with IL-6 receptor (IL-6R) in the presence of IL-6. Soluble forms of gp130 (sgp130) with molecular weights of 90 and 110 Kd were found in human serum. In the presence of recombinant IL- 6 (rIL-6), serum sgp130 were capable of associating with serum sIL-6R. By the sandwich enzyme-linked immunosorbent assay, healthy human sera was shown to contain 390 +/- 72 ng/mL of sgp130. A mouse pro-B-cell line-derived transfectant, BAF-130, expressing human gp130 was used to examine the function of serum sgp130. When supplemented with rIL-6, human serum induced DNA synthesis in BAF-130 cells, whereas the serum deprived of sIL-6R did not. In contrast, the DNA synthesis induced in BAF-130 cells by rIL-6-supplemented serum was increased when the serum was deprived of sgp130. These results indicated that serum sgp130 could negatively regulate the IL-6 signal. Recently, gp130 has been shown to be involved in the signaling processes of oncostatin M, leukemia inhibitory factor, and ciliary neurotropic factor, in addition to those of IL-6. Recombinant sgp130 showed inhibitory effect on the biologic function of such cytokines. This work implies physiologic roles of naturally produced serum sgp130 in modulating signals through gp130.

Both normal somatic stem cells and cancer cells are thought to be capable of unlimited proliferation. Paradoxically, however, some cancers seem to contain stem-like cells (cancer stem cells). There is increasing evidence that cancers might contain their own stem cells. Many cancers, like normal organs, seem to be maintained by a hierarchical organization that includes slowly dividing stem cells,rapidly dividing transit amplifying cells (precursor cells), and differentiated cells. Malignant gliomas, for example,often contain both undifferentiated and differentiated cells and sometimes contain cells that express neuronal markers as well as cells that express glial markers, suggesting that they may contain multipotent neural stem cell-like cells. We have shown that some cancer cell lines contain a small side population (SP), which, in many normal tissues, is thought to contain the stem cells of the tissue. We provide evidence that SP cells in the C6 glioma cell line can produce both neurons and glial cells and thus have cancer stem cell property. Taken together with studies on normal neural stem cells, studies on cancer stem cells will help us to understand a link between normal stem cells and cancer stem cells.