Ren Peng, Sun Deshun, Xin Dajiang, Ma Wanli, Chen Peng, Gao Hongwei, Zhang Shouqiang, Gong Mingzhi
Department of Osteology, The Second Hospital, Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Osteology, Zhangqiu City Hospital of Traditional Chinese Medicine, Jinan, Shandong 250200, P.R. China.
Mol Med Rep. 2014 Dec;10(6):3106-12. doi: 10.3892/mmr.2014.2635. Epub 2014 Oct 14.
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.
血清淀粉样蛋白A（SAA）被认为是一种参与肿瘤进展和转移的重要急性期蛋白。然而，目前尚无证据表明其参与骨肉瘤。本研究旨在探讨SAA对骨肉瘤细胞侵袭的影响。分别采用划痕伤口愈合试验和Transwell试验检测SAA对骨肉瘤细胞迁移和侵袭的影响。在U2OS细胞中检测αvβ3整合素在蛋白质和mRNA水平的表达。使用甲酰肽受体样1（FPRL-1）、丝裂原活化蛋白激酶和αvβ3整合素的激动剂、抑制剂或小干扰RNA（siRNA）来研究SAA对U2OS细胞迁移和侵袭调控作用的潜在机制。本研究表明，SAA促进骨肉瘤细胞迁移和侵袭。SAA以浓度和时间依赖性方式上调αvβ3整合素的表达。当用其拮抗剂抑制αvβ3整合素时，U2OS细胞的迁移和侵袭能力明显受到抑制。用siRNA和抑制剂抑制FPRL-1可显著下调SAA诱导的αvβ3整合素产生。本研究还发现，细胞外信号调节激酶（ERK）1/2而非c-Jun氨基末端激酶或p38在此过程中起重要作用。这些发现表明，SAA通过FPRL-1/ERK/αvβ3整合素途径调节骨肉瘤细胞的迁移和侵袭。
