No abstract

Osteosarcoma (OS) is a primary bone malignancy with a high early metastatic propensity. It is crucial to find specific protein targets to develop therapeutic strategies against this lethal disease. Tetraspanin CD151 is involved in facilitating tumor metastasis. However, the role and molecular mechanism of CD151 in promoting OS metastasis remain enigmatic. In the present study, we used small interfering RNA (siRNA) to inhibit CD151 expression in highly metastatic OS cells and the results demonstrated that CD151 knockdown inhibited their migration, invasion and metastasis. We further investigated the molecular mechanism of CD151 by inhibiting genes known to be involved in metastasis in OS cells and found that CD151 modulated matrix metalloproteinase 9 (MMP9) expression through the glycogen synthase kinase 3 (GSK-3β)/β-catenin signaling pathway. We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS. This suggests that CD151 may be a useful antimetastatic target for OS.

Interleukin-10 (IL-10) is a multifunctional cytokine that participates in the development and progression of various malignant tumors. However, data regarding the role of IL-10 polymorphisms in osteosarcoma development are not available. A case-control study was conducted in 260 patients with osteosarcoma and 260 healthy controls to investigate the possible association between IL-10 polymorphisms and the risk of osteosarcoma. Our results indicate the IL-10 -1082A/G (rs1800896) polymorphism is significantly associated with an increased risk of osteosarcoma in all genetic models (AG vs. AA, odds ratio (OR) = 1.56; 95 % confidence interval (CI) = 1.28-2.32, P = 0.017; GG vs. AA, OR = 1.62, 95 % CI 1.24-2.61, P = 0.013; AG + GG vs. CC, OR = 1.76, 95 % CI = 1.31-3.01, P = 0.019). However, the genotype and allele frequencies of IL-10 -819C/T (rs1800871) and -592A/C (rs1800872) polymorphisms in osteosarcoma patients did not significantly differ from controls. Further analyses revealed that the IL-10 -1082A/G (rs1800896) genotypes were associated with advanced tumor stages and metastasis in osteosarcoma patients. Additionally, a statistically significant association between the IL-10 -1082A/G (rs1800896) genotype and poor survival in osteosarcoma patients was observed. Our results demonstrate that the IL-10 -1082A/G (rs1800896) genotype is associated with an increased susceptibility and worse outcome for osteosarcoma patients in the Chinese Han population.