Abstract
Accumulating evidences indicate the elevated expression of αB-Crystallin (Cryab) is implicated in tumorigenesis. However, the expression and biologic role of Cryab in osteosarcoma (OS) are still unknown. In this study, we showed that Cryab expression was elevated in OS tissues and cell lines, and down-regulation of Cryab in MG-63 and U-2OS cells led to a decline in the cells’ aggressiveness, and reduced secretion of matrix metalloproteinase-9 (MMP-9) in vitro, and lower metastasis potential in vivo. Further study indicated that the Cryab expression was positively associated with the activity of ERK1/2 which is responsible for the cells’ aggressiveness and MMP-9 secretion. Clinically, our data confirmed that the high level of Cryab was associated with shorten survival and tumor recurrence for the postoperative OS patients. Together, our results indicate that high level of Cryab is a new adverse outcomes marker for OS patients and may be used as a new therapeutic target.
Highlights
Osteosarcoma (OS) is the most frequent malignant bone tumor in children and young people [1]
The overall survival of patients with high-grade OS has been markedly improved over the past decades [2], the recurrence for this disease still occurs in approximately 30 - 40 percent of patients with non-metastatic OS, almost 80 percent of the OS patients with metastasis at the time of diagnosis will recur [3, 4]
The up-regulation of Cryab expression seems to be associated with oncogenic transformation in basallike breast cancer, and induces hepatocellular carcinoma cells epithelial-mesenchymal transition [9], In addition, the high level of Cryab was reported to be associated with cell apoptosis resistance, enhance cell survival under the oncogenic stress, growth factor starvation, chemotherapy, and other cellular stressors [12]
Summary
Osteosarcoma (OS) is the most frequent malignant bone tumor in children and young people [1]. The increasing expression of Cryab have been identified to be related to a number of pathologies including cancer, with elevated expression of Cryab observed in several cancers, for example, a high level of Cryab has been found to be a prognostic marker in breast, renal, thyroid, nasopharyngeal, hepatocellular and lung cancers [8,9,10,11]. The up-regulation of Cryab expression seems to be associated with oncogenic transformation in basallike breast cancer, and induces hepatocellular carcinoma cells epithelial-mesenchymal transition [9], In addition, the high level of Cryab was reported to be associated with cell apoptosis resistance, enhance cell survival under the oncogenic stress, growth factor starvation, chemotherapy, and other cellular stressors [12]. Given the key role of Cryab in human cancers development, further study of the role and mechanism of Cryab in OS is urgently needed
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