| Gpl30 is a kind of glucoprotein with 130KD. A homo-dimer or hetero-dimer comprised with gp!30 and a series of cytokine receptors, including IL-6, LIF, CNTF, or IL-11 receptors, after they combine with the respective cytokines. Then the signal transduction pathway of gp!30 is activated and a signal, which induces the proliferation and survival of cell, is transduced into nuclear. Thus gp!30 is the common signal transduction molecule. Gpl30 molecule expresses universally on many tissues including immune system, hemapoietic system, and nerve system. Gpl30 has an essential role in the function and regulation of the above systems, especially in the development of hemapoietic system. The signal transduced by gp!30 is necessary during the differentiation and proliferation of hemapoietic cells. It is evidenced that the embryo of gp!30 gene-knockout mouse was dead due to a serious impediment of the development of hemapoietic system. Meanwhile, gp!30 related signal transduction pathway and cytokine/recptors take a very important role in some pathological courses.Multiple myeloma (MM) is a kind of malignant plasma cell disease. It is proved that the paracrine and autocrine gp!30-related cytokines, such as IL-6, is essential for the proliferation and growth of myeloma cells. MM cells will stop proliferating and become apoptosis if the signal of gp!30 is absent in culture system. It is found that there is a high level of IL-6 in serum of patients with myeloma in clinic research. Anti-IL-6 neutralizing monoclonal antibody (mAb) could block the proliferation of myeloma cells and induced the apoptosis of the myeloma cells in vitro. And this mAb could also improve the symptom in some patients with myeloma in clinic experimental uses.It is shown that gp130 pathway also could be activated by other cytokine/receptors, such as IL-11, OSM, LIF, CNTF and their receptors. Furthermore,gp130 may be a co-signal transduction molecule for other cytokine/receptors. In this study, we found an overexpression of gp130 and gpISO-related cytokine/receptors and an overexpression of EGF/EGF receptor family members in IL-6 dependent myeloma cell lines, XGs, and fresh myeloma cells by using ATLAS DNA microarray analysis. The overexpression of IL-6, HB-EGF, and EGFR in myeloma cell lines was proved by RT-PCR and/or Flow cytometery. It was found that HB-EGF could support the growth of XGs cells even IL-6 was absent in culture, and an inhibitor of HB-EGF, CRM197, could block the proliferation of XG cells induced by IL-6. Interestingly, either anti-IL-6 or anti-gp!30 neutralizing mAb could blcok the proliferation of myeloma cells induced by IL-6 or HB-EGF. It suggests that the cooperation between HB-EGF/erbBl autocrine loop and IL-6/gpl30 autocrine loop is essential in the proliferation and growth of myeloma cells. In the clinic treatment of myeloma, it showed that anti-IL-6 mAb alone could not have a perfect therapy effect when the patient is with a high level of IL-6 in their body. And this is due to a relative low level of mAb in patient. In this study, we found that a low concentration anti-IL-6 mAb was efficient to block the proliferation of myeloma cells in vitro if anti-erbB 1 mAb was used together. Thus the combination use of these two mAb may have a great potential value in clinic.At the same time, dendritic cells (DC), which can uptake, process, and present antigen signal to T cells in vivo, are one of the most important kind of antigen presentation cells (APC). It showed that myeloma cells can secrete a large amount of Id+Ig, which is a good target tumor specific antigen that can be present by DC. In this case, it is thought that DC treatment could be an efficient way to treat MM. It is essential for DC treatment to produce enough functional DC in vitro since it is very difficult to isolate and purify DC, which is very scare and short of specific surface markers. In order to explore the role of gplSO-linked signal transduction in the differentiation and maturation of dendritic cells (DC), the monoclonal antibody (mAb), B-S12, an ag...
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