Serum amyloid A promotes osteosarcoma invasion via upregulating αvβ3 integrin

Ren,Peng; Sun,Deshun; Xin,Dajiang; Ma,Wanli; Chen,Peng; Gao,Hongwei; Zhang,Shouqiang; Gong,Mingzhi

doi:10.3892/mmr.2014.2635

Serum amyloid A promotes osteosarcoma invasion via upregulating αvβ3 integrin

Authors:
- Peng Ren
- Deshun Sun
- Dajiang Xin
- Wanli Ma
- Peng Chen
- Hongwei Gao
- Shouqiang Zhang
- Mingzhi Gong
View Affiliations

Affiliations: 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, Department of Osteology, Mount Yantai Hospital, Yantai, Shandong 264000, P.R. China
Published online on: October 14, 2014 https://doi.org/10.3892/mmr.2014.2635
Pages: 3106-3112

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Murphey MD, Robbin MR, McRae GA, Flemming DJ, Temple HT and Kransdorf MJ: The many faces of osteosarcoma. Radiographics. 17:1205–1231. 1997. View Article : Google Scholar : PubMed/NCBI
2	Allison DC, Carney SC, Ahlmann ER, Hendifar A, Chawla S, Fedenko A, et al: A meta-analysis of osteosarcoma outcomes in the modern medical era. Sarcoma. 2012:7048722012. View Article : Google Scholar : PubMed/NCBI
3	Mirabello L, Troisi RJ and Savage SA: Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 115:1531–1543. 2009. View Article : Google Scholar : PubMed/NCBI
4	Assi H, Missenard G, Terrier P, Le Pechoux C, Bonvalot S, Vanel D, et al: Intensive induction chemotherapy without methotrexate in adult patients with localized osteosarcoma: results of the Institut Gustave-Roussy phase II trial. Curr Oncol. 17:23–31. 2010. View Article : Google Scholar
5	Balkwill F and Mantovani A: Inflammation and cancer: back to Virchow? Lancet. 357:539–545. 2001. View Article : Google Scholar : PubMed/NCBI
6	Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI
7	Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar
8	Cole SW: Chronic inflammation and breast cancer recurrence. Journal Clinical Oncology. 27:3418–3419. 2009. View Article : Google Scholar : PubMed/NCBI
9	Crawford S: Anti-inflammatory/antioxidant use in long-term maintenance cancer therapy: A new therapeutic approach to disease progression and recurrence. Ther Adv Med Oncol. 6:52–68. 2014. View Article : Google Scholar : PubMed/NCBI
10	Noh K, Kim KO, Patel NR, Staples JR, Minematsu H, Nair K, et al: Targeting inflammatory kinase as an adjuvant treatment for osteosarcomas. J Bone Joint Surg Am. 93:723–732. 2011. View Article : Google Scholar : PubMed/NCBI
11	Liu C, Pan C, Shen J, Wang H and Yong L: Identification of serum amyloid A in the serum of gastric cancer patients by protein expression profiling. Oncol Lett. 3:1259–1262. 2012.PubMed/NCBI
12	Mittal A, Poudel B, Pandeya DR, Gupta SP, Sathian B and Yadav K: Serum amyloid a as an independent prognostic factor for renal cell carcinoma - a hospital based study from the Western region of Nepal. Asian Pac J Cancer Prev. 13:2253–2255. 2012. View Article : Google Scholar
13	Zhang G, Sun X, Lv H, Yang X and Kang X: Serum amyloid A: A new potential serum marker correlated with the stage of breast cancer. Oncol Lett. 3:940–944. 2012.PubMed/NCBI
14	Desgrosellier JS and Cheresh DA: Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 10:9–22. 2010. View Article : Google Scholar : PubMed/NCBI
15	Desai B, Rogers MJ and Chellaiah MA: Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells. Mol Cancer. 6:182007. View Article : Google Scholar
16	Sung V, Stubbs JT 3rd, Fisher L, Aaron AD and Thompson EW: Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the alpha(v)beta3 and alpha(v)beta5 integrins. J Cell Physiol. 176:482–494. 1998. View Article : Google Scholar
17	Pecheur I, Peyruchaud O, Serre CM, Guglielmi J, Voland C, Bourre F, et al: Integrin alpha(v)beta3 expression confers on tumor cells a greater propensity to metastasize to bone. FASEB J. 16:1266–1268. 2002.PubMed/NCBI
18	Tome Y, Kimura H, Maehara H, Sugimoto N, Bouvet M, Tsuchiya H, et al: High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of alphavbeta3 integrin. Anticancer Res. 33:3623–3627. 2013.
19	Kurihara Y, Nakahara T and Furue M: alphaVbeta3-integrin expression through ERK activation mediates cell attachment and is necessary for production of tumor necrosis factor alpha in monocytic THP-1 cells stimulated by phorbol myristate acetate. Cell Immunol. 270:25–31. 2011. View Article : Google Scholar
20	Furundzija V, Fritzsche J, Kaufmann J, Meyborg H, Fleck E, Kappert K, et al: IGF-1 increases macrophage motility via PKC/p38-dependent alphavbeta3-integrin inside-out signaling. Biochem Biophys Res Commun. 394:786–791. 2010. View Article : Google Scholar : PubMed/NCBI
21	Li B, Dong Z, Liu H, Xia YF, Liu XM, Luo BB, et al: Serum amyloid A stimulates lipoprotein-associated phospholipase A2 expression in vitro and in vivo. Atherosclerosis. 228:370–379. 2013. View Article : Google Scholar
22	Dong Z, An F, Wu T, Zhang C, Zhang M, Zhang Y, et al: PTX3, a key component of innate immunity, is induced by SAA via FPRL1-mediated signaling in HAECs. J Cell Biochem. 112:2097–2105. 2011. View Article : Google Scholar : PubMed/NCBI
23	Levinson H, Hopper JE and Ehrlich HP: Overexpression of integrin alphav promotes human osteosarcoma cell populated collagen lattice contraction and cell migration. J Cell Physiol. 193:219–224. 2002. View Article : Google Scholar : PubMed/NCBI
24	Uhlar CM and Whitehead AS: Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem. 265:501–523. 1999. View Article : Google Scholar : PubMed/NCBI
25	Tölle M, Huang T, Schuchardt M, Jankowski V, Prufer N, Jankowski J, et al: High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A. Cardiovasc Res. 94:154–162. 2012.PubMed/NCBI
26	d’Eril GM, Anesi A, Maggiore M and Leoni V: Biological variation of serum amyloid A in healthy subjects. Clin Chem. 47:1498–1499. 2001.PubMed/NCBI
27	Shattil SJ, Kim C and Ginsberg MH: The final steps of integrin activation: the end game. Nat Rev Mol Cell Biol. 11:288–300. 2010. View Article : Google Scholar : PubMed/NCBI
28	Duan X, Jia SF, Zhou Z, Langley RR, Bolontrade MF and Kleinerman ES: Association of alphavbeta3 integrin expression with the metastatic potential and migratory and chemotactic ability of human osteosarcoma cells. Clin Exp Metastasis. 21:747–753. 2004. View Article : Google Scholar
29	Song C, Hsu K, Yamen E, Yan W, Fock J, Witting PK, et al: Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes. Atherosclerosis. 207:374–383. 2009. View Article : Google Scholar : PubMed/NCBI
30	Pechkovsky DV, Scaffidi AK, Hackett TL, Ballard J, Shaheen F, Thompson PJ, et al: Transforming growth factor beta1 induces alphavbeta3 integrin expression in human lung fibroblasts via a beta3 integrin-, c-Src-, and p38 MAPK-dependent pathway. J Biol Chem. 283:12898–12908. 2008. View Article : Google Scholar : PubMed/NCBI