This suggests that a) the SSTRs expression is found along the B cell differentiation stages b) SSTRs expression is not modulated during this process b) SSTRs expression pattern

is not a marker for B cell differentiation. Sst and its analogs have been demonstrated to negatively regulate tumor cell proliferation (see for review [42]) and have been used in inoperable patients where neuroendocrine tumours stabilization or shrinkage can be obtained Staurosporine solubility dmso [43]. However, in other cancers such as hepatocellular carcinoma, the SIS3 molecular weight clinical benefit of Oct is not evidenced even in positive Oct scintigraphy patients [44]. To our knowledge, only one study examined the effects of Sst and Oct in MM cell lines and showed a strong decrease of viable cells after 48 h Oct exposure [41]. This is in marked contrast with our data since either Sst or Oct were unable to affect

cell proliferation of the U266 cell line. Such discrepancies should be explained by the use of different clones of the U266. We can also hypothesize that our U266 cells would express SSTRs with opposite effects on proliferation. SSTR2 and 5 were reported to inhibit cell proliferation by phosphotyrosine phosphatase (PTP) activation and inhibition of calcium channels, respectively [42, 45]. In contrast, SSTR4 were shown to activate the MAPK cascade and promoting proliferation [46]. So, no effect on proliferation would be observed upon co-activation of those SSTRs. Discrepancies between our study and the one of Georgii-Hemming and collaborators [41] about Bortezomib manufacturer Chlormezanone cellular viability should also be due to the presence or the absence of serum in the culture medium. However, we can rule out such explanation since we observed no effect upon SSTR agonists when experiments were conducted in serum-free culture medium (data not shown). Anti-tumoral activity of Sst or its analogs are also due to pro-apoptotic effects (see for review [47]). In two MM cell lines U266 (current study) and LP-1 (data not shown), we observed that neither Sst nor Oct promote apoptosis in our experimental

conditions. This was illustrated by the lack of sub-G1 peak in cell cycle assay and the absence of labelling in annexin V/PI experiments. In contrast, Georgii-Hemming et al. showed that in three MM cells (HL-407L, HL-407E and U-1958) Oct induced a weak increase in annexin V/PI staining suggesting that SSTRs could promote apoptosis [41] but the U266 cell line was not investigated. Sharma et al. first described the role of SSTR3 in apoptosis when expressed in Chinese hamster ovary cells and demonstrated that Oct promotes dephosphorylation of wild-type p53 which leads to DNA fragmentation [35]. Even in the absence of apoptosis, we can not rule out that SSTRs are not coupled to apoptotic pathways since U266 was shown to express the anti-apoptotic protein Bcl-2 [48].