Serum amyloid A (SAA) is regarded as an important acute phase protein involved in tumor progression and metastasis. However, at present there is no evidence of its involvement in osteosarcoma. The present study aimed to investigate the effect of SAA on the invasion of osteosarcoma cells. The effects of SAA on the migration and invasion of osteosarcoma cells were detected using scratch wound healing and transwell assays, respectively. The expression of αvβ3 integrin was detected at the protein and mRNA levels in U2OS cells. Agonists, inhibitors or siRNA of formyl peptide receptor like‑1 (FPRL‑1), mitogen‑activated protein kinases and αvβ3 integrin were used to investigate the mechanism underlying the effects of SAA on the regulation of U2OS cell migration and invasion. The present study revealed that SAA promoted osteosarcoma cell migration and invasion. SAA upregulated the expression of αvβ3 integrin in a concentration‑ and time‑dependent manner. When inhibiting αvβ3 integrin with its antagonist, the migration and invasion abilities of the U2OS cells were markedly inhibited. SAA‑induced αvβ3 integrin production was significantly downregulated by inhibiting FPRL‑1 with siRNA and inhibitors. The present study also found that extracellular signal‑regulated kinase (ERK) 1/2, but not c‑Jun N‑terminal kinase or p38, was important in this process. These findings demonstrated that SAA regulated osteosarcoma cell migration and invasion via the FPRL‑1/ERK/αvβ3 integrin pathway.

Background Osteosarcoma (OS) is the most common malignant bone cancer with more metastasis and increased occurrence in children and teen-agers and being responsible for more number of morbidity and mortality worldwide. Objective The current exploration was planned study the in vitro anticancer actions of dieckol against human OS MG-63 cells via PI3K/AKT/mTOR signaling inhibition. Methodology The cytotoxicity of dieckol was scrutinized by MTT assay. Effects of dieckol on the ROS accumulation, apoptotic cell death, and MMP level in the MG-63 cells were studied by respective fluorescence staining assays. The levels of proliferative, inflammatory, and apoptotic markers in the dieckol treated MG-63 cells were scrutinized by marker specific kits. The expressions of PI3K, AKT, and mTOR was assayed by RT-PCR. Results The MTT assay revealed that the dieckol dose dependently prevented MG-63 cells viability and the IC50 was found at 15 µM. Dieckol treatment effectively reduced the MMP level and improved the ROS generation and apoptosis in MG-63 cells. Dieckol also regulated the proliferative (cyclin D1), inflammatory (COX-2, IL-6, TNF-α, and NF-κB), and apoptotic (caspase-3, Bax, Bcl-2) markers in the MG-63 cells. The PI3K/AKT/mTOR signaling in the MG-63 cells were effectively inhibited by the dieckol treatment. Conclusion In conclusion, our findings from this study recommends that the dieckol could be a talented anticancer candidate for the OS management in the future.

No abstract

Increased expression of cancer/testis antigens (CTAs) is reported in various tumors. However, the unique role of CTAs in tumor genesis has not yet been verified. Here, we first report the functional role of CT45A1 in the carcinogenesis of osteosarcoma. RNA sequencing and immunohistochemistry confirmed that elevated expression of CT45A1 was detected in osteosarcoma, especially in metastatic tissues of osteosarcoma. Furthermore, osteosarcoma patients with poorer prognosis showed high expression of CT45A1. In cell tests, CT45A1 overexpression was shown to strengthen the proliferation, migration, and invasion abilities of osteosarcoma cells, while silencing CT45A1 markedly elicited the opposite effects in these tests by disrupting the activation of β-catenin. In summary, we identify a novel role of CT45A1 in osteosarcoma. Furthermore, our results suggested that CT45A1 may contribute to the development of osteosarcoma and could be a possible therapeutic target for osteosarcoma patients.

No abstract