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In addition, syndecan 1 binds HGF within the surface of myeloma cells bringing HGF in near proximity of its receptor c Met. Immunohistochemical staining for HGF on bone marrow biopsies uncovered that plasma cells from practically all myeloma individuals stained good for HGF.

That is in line with other reports indicating that boost of c Met expression enhances both the biologic effects of HGF and c Met signaling in different cell kinds. A recent publication also indicates that the level of c Met expression is essential for your survival of myeloma cells as partly downregulation of c Met lead to myeloma cell death. In addition, in vivo induction Cabozantinib of the IGF 1 receptor has been reported in the murine myeloma model 5T33MM, and this induction was necessary for biological effects of IGF 1 in these experiments. Inhibiting c Met had substantial effects on IL 6induced proliferation in four out of nine primary samples, although the frequency of this mechanism in primary myeloma patients is hard to estimate due to the low numbers of samples.

Further studies are necessary to see, NSCLC if hyperdiploid patients with high HGF and IL 6 expression are subjected to synergy between IL 6 and HGF, and if they can benet from c Met inhibition. The potentiating effect of c Met signaling in IL 6induced p44 42 MAPK activation in ANBL 6 cells was intriguing and a novel observation. Neither HGF nor IL 6 alone could induce Ras MAPK signaling, but the combination of HGF and IL 6 was necessary to activate this pathway. The Ras MAPK pathway is a major regulator of cell proliferation, and has previously been shown to be important for myeloma cell proliferation in vitro and in vivo. However, the role of c Met as a regulator of IL 6 induced Ras MAPK signaling has to our knowledge not been shown in myeloma cells before.

NSC 87877 is also known to inhibit the tyrosine phosphatase Shp1, however, Shp1 has been shown to negatively control receptor signaling, and even to reduce MAPK activation in thyroid carcinoma and neurons. Here, we show that c Met signaling may be important in myeloma cell proliferation induced by IL 6.