Anti-SS18 polyclonal antibody

To clarify the clinicopathological and biological role of SS18 and beta-catenin in synovial sarcoma, our results showed that SS18 and beta-catenin expression were upregulated in synovial sarcoma cells and tissues. SS18 positive expression was significantly associated with primary tumor location (P<0.05). The 5-year OS rate (22.0%) for patients with SS18 positive expression was less than that (38.4%) for patients with SS18 negative expression. Significant positive correlation between SS18 expression and beta-catenin abnormal expression was found in synovial sarcoma tissues (P=0.004). SS18 knockdown dramatically inhibited cellular proliferation, colony formation, and migration, but induced G1 phase arrest and apoptosis in SW982 cells. Further study showed that SS18 knock-down dramatically suppressed beta-catenin and its down-stream genes expression in SW982 cells. Interestingly, beta-catenin knock-down dramatically suppressed SS18 expression in SW982 cells. Wnt-3a and DKK1 increased and suppressed nuclear and cytoplasmic SS18 expression in SW982 cells, respectively. Most importantly, a direct interaction of SS18 and beta-catenin was found in SW982 cells. beta-catenin transcriptional activity significantly increased in SW982 cells transfected with SS18 expression plasmid. In conclusion, our findings first indicate that the interaction of SS18 and beta-catenin might play a crucial role in tumorigenesis and progression of synovial sarcoma.

Synovial sarcomas are aggressive soft-tissue malignancies that express chromosomal translocation-generated fusion genes, SS18-SSX1 or SS18-SSX2 in most cases. Here, we report a mouse sarcoma model expressing SS18-SSX1, complementing our prior model expressing SS18-SSX2. Exome sequencing identified no recurrent secondary mutations in tumors of either genotype. Most of the few mutations identified in single tumors were present in genes that were minimally or not expressed in any of the tumors. Chromosome 6, either entirely or around the fusion gene expression locus, demonstrated a copy number gain in a majority of tumors of both genotypes. Thus, by fusion oncogene coding sequence alone, SS18-SSX1 and SS18-SSX2 can each drive comparable synovial sarcomagenesis, independent from other genetic drivers. SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences overall. In direct tumorigenesis comparisons, SS18-SSX2 was slightly more sarcomagenic than SS18-SSX1, but equivalent in its generation of biphasic histologic features. Meta-analysis of human synovial sarcoma patient series identified two tumor-gentoype-phenotype correlations that were not modeled by the mice, namely a scarcity of male hosts and biphasic histologic features among SS18-SSX2 tumors. Re-analysis of human SS18-SSX1 and SS18-SSX2 tumor transcriptomes demonstrated very few consistent differences, but highlighted increased native SSX2 expression in SS18-SSX1 tumors. This suggests that the translocated locus may drive genotypephenotype differences more than the coding sequence of the fusion gene created. Two possible roles for native SSX2 in synovial sarcomagenesis are explored. Thus, even specific partial failures of mouse genetic modeling can be instructive to human tumor biology.