One Disappointing Belief About MAPK Unwrapped

In contrast, ES, OS, or CS cell lines in culture expressed 10- to 100-fold less OSM mRNA (except one CS cell line), suggesting either an induced production in vivo or a production by nontumor cells. To discriminate between these possibilities, OSM expression was next analyzed in human tumors developed in nude mice (xenografts). Species-specific PCR allowed us to quantify human OSM (produced by tumor cells) and murine Osm (produced by host cells). Human OSM was LY2109761 ic50 not detected in five different ES or OS xenografts, whereas murine Osm was detected in four of five tumors ( Figure 5D). By IHC on patient biopsy specimens, OSM was detected in three of three ES, three of three OS, and one of three CS cells studied. OSM staining was observed close to or inside vascular vessels, with one ES biopsy specimen (patient 1) showing positive myofibroblasts MAPK ( Figure 5E). Cancer cells or macrophages were never positive. The expression of LIF, OSM, their receptor subunits, and MYC was also analyzed in a large panel of patient biopsy specimens using cDNA arrays. The OSMR transcript appeared to be expressed threefold less in ESs compared with OSs (P = 4 �� 10?7), whereas LIFR mRNA was expressed at a similar level in these two types of tumor ( Figure 6A). When compared with other tumors (pediatric or not) or normal tissues, the LIFR/OSMR analysis revealed a striking homology between ES and other tumors with (neuro)ectodermic features (glioma, medulloblastoma, or neuroblastoma) and tissues of the central nervous system ( Figure 6B; see also Supplemental Figure S4 at http://ajp.amjpathol.org). OSs, most other tumors with mesodermic features (liposarcoma, leiomyosarcoma, gastrointestinal stromal tumor, and undifferentiated sarcoma), MSCs, and carcinomas (lung cancer and renal cell carcinoma) appeared to express a significantly higher level of OSMR. The expression of LIFR was more variable within each group, with Selleckchem EPZ5676 the highest expression being observed in ESs, gliomas, OSs, and renal cell carcinomas. In correlation with the low OSMR expression, the expression of LIF and IL-6 appeared low in ectodermic tumors compared with mesodermic tumors or carcinomas. There was no significant difference in OSM mRNA expression between ectodermic tumors, mesodermic tumors, and carcinomas, but its expression was higher in hematopoietic cells (see Supplemental Figure S4 at http://ajp.amjpathol.org). When accounting for all samples (n = 943), we found that LIF or IL-6 expression positively correlated with OSMR expression (r = 0.491, P