Visfatin promotes osteosarcoma cell migration and invasion via induction of epithelial-mesenchymal transition

Cheng,Gong; Liu,Changying; Sun,Xiujiang; Zhang,Lei; Liu,Lifang; Ouyang,Jun; Li,Bo

doi:10.3892/or.2015.4053

Visfatin promotes osteosarcoma cell migration and invasion via induction of epithelial-mesenchymal transition

Authors:
- Gong Cheng
- Changying Liu
- Xiujiang Sun
- Lei Zhang
- Lifang Liu
- Jun Ouyang
- Bo Li
View Affiliations

Affiliations: Department of Anatomy, Southern Medical University, Guangzhou, Guangdong, P.R. China, Department of Orthopedics, People's Hospital of Linyi City, Linyi, Shandong, P.R. China, Department of Sports Medicine, Yantaishan Hospital, Yantai, Shandong, P.R. China, Department of Gastroenterology, Central Hospital of Zibo, Zibo, Shandong, P.R. China, Department of Cardiology, Central Hospital of Zibo, Zibo, Shandong, P.R. China
Published online on: June 11, 2015 https://doi.org/10.3892/or.2015.4053
Pages: 987-994

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

Visfatin is considered to be a biomarker in various types of cancers. However, no evidence has been reported for the direct effect of visfatin on osteosarcoma cell metastasis. The aims of the present study were to investigate the influence of visfatin on the migration and invasion of osteosarcoma cells and clarify the underlying mechanism. The expression levels of epithelial-mesenchymal transition (EMT) markers, as well as the transcriptional factor Snail-1, were first detected at both the protein and mRNA levels in U2OS osteosarcoma cells after stimulation of visfatin. Then the expression of NF-κB (p65) was detected by western blot analysis, and siRNA of Snail-1 and inhibitor of NF-κB were used to investigate the effect of visfatin. Finally, migration and invasion of the cells were detected respectively by scratch wound healing and transwell assays. Visfatin downregulated E-cadherin and upregulated N-cadherin in concentration- and time-dependent manners at the protein and mRNA levels. The expression of Snail-1 was also upregulated. Moreover, visfatin also promoted the nuclear translocation of the NF-κB pathway. Administration of siRNA of Snail-1 and the inhibitor BAY11-7082 validated the roles of Snail-1 and NF-κB in the visfatin-induced regulation of EMT markers. Migration and invasion of U2OS osteosarcoma cells were promoted following the application of visfatin. These results demonstrated that visfatin enhances the migration and invasion of osteosarcoma cells via the NF-κB/Snail-1/EMT pathway.

View Figures

View References

1	Link MP, Goorin AM, Miser AW, Green AA, Pratt CB, Belasco JB, Pritchard J, Malpas JS, Baker AR, Kirkpatrick JA, et al: The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 314:1600–1606. 1986. View Article : Google Scholar : PubMed/NCBI
2	Luu HH, Zhou L, Haydon RC, Deyrup AT, Montag AG, Huo D, Heck R, Heizmann CW, Peabody TD, Simon MA, et al: Increased expression of S100A6 is associated with decreased metastasis and inhibition of cell migration and anchorage independent growth in human osteosarcoma. Cancer Lett. 229:135–148. 2005. View Article : Google Scholar : PubMed/NCBI
3	Dalamaga M: Nicotinamide phosphoribosyl-transferase/visfatin: A missing link between overweight/obesity and postmenopausal breast cancer? Potential preventive and therapeutic perspectives and challenges. Med Hypotheses. 79:617–621. 2012. View Article : Google Scholar : PubMed/NCBI
4	Hufton SE, Moerkerk PT, Brandwijk R, de Bruïne AP, Arends JW and Hoogenboom HR: A profile of differentially expressed genes in primary colorectal cancer using suppression subtractive hybridization. FEBS Lett. 463:77–82. 1999. View Article : Google Scholar : PubMed/NCBI
5	Folgueira MA, Carraro DM, Brentani H, Patrão DF, Barbosa EM, Netto MM, Caldeira JR, Katayama ML, Soares FA, Oliveira CT, et al: Gene expression profile associated with response to doxorubicin-based therapy in breast cancer. Clin Cancer Res. 11:7434–7443. 2005. View Article : Google Scholar : PubMed/NCBI
6	Bi TQ and Che XM: Nampt/PBEF/visfatin and cancer. Cancer Biol Ther. 10:119–125. 2010. View Article : Google Scholar : PubMed/NCBI
7	Hay ED: The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn. 233:706–720. 2005. View Article : Google Scholar : PubMed/NCBI
8	Haslehurst AM, Koti M, Dharsee M, Nuin P, Evans K, Geraci J, Childs T, Chen J, Li J, Weberpals J, et al: EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer. BMC Cancer. 12:912012. View Article : Google Scholar : PubMed/NCBI
9	Rosanò L, Cianfrocca R, Spinella F, Di Castro V, Nicotra MR, Lucidi A, Ferrandina G, Natali PG and Bagnato A: Acquisition of chemoresistance and EMT phenotype is linked with activation of the endothelin A receptor pathway in ovarian carcinoma cells. Clin Cancer Res. 17:2350–2360. 2011. View Article : Google Scholar : PubMed/NCBI
10	Zhang XC, Chen JQ and Li B: Salvianolic acid A suppresses CCL-20 expression in TNF-α-treated macrophages and ApoE-deficient mice. J Cardiovasc Pharmacol. 64:318–325. 2014. View Article : Google Scholar : PubMed/NCBI
11	Bae KM, Parker NN, Dai Y, Vieweg J and Siemann DW: E-cadherin plasticity in prostate cancer stem cell invasion. Am J Cancer Res. 1:71–84. 2011.PubMed/NCBI
12	Pon YL, Auersperg N and Wong AS: Gonadotropins regulate N-cadherin-mediated human ovarian surface epithelial cell survival at both post-translational and transcriptional levels through a cyclic AMP/protein kinase A pathway. J Biol Chem. 280:15438–15448. 2005. View Article : Google Scholar : PubMed/NCBI
13	Li B, Dong Z, Liu H, Xia YF, Liu XM, Luo BB, Wang WK, Li B, Gao F, Zhang C, 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 : PubMed/NCBI
14	Peinado H, Olmeda D and Cano A: Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype? Nat Rev Cancer. 7:415–428. 2007. View Article : Google Scholar : PubMed/NCBI
15	Zhao Z, Wu MS, Zou C, Tang Q, Lu J, Liu D, Wu Y, Yin J, Xie X, Shen J, et al: Downregulation of MCT1 inhibits tumor growth, metastasis and enhances chemotherapeutic efficacy in osteosar-coma through regulation of the NF-κB pathway. Cancer Lett. 342:150–158. 2014. View Article : Google Scholar
16	Li Y, Zhang ZN, Zhao HM, Tong ZC, Yang J, Wang H and Liang XJ: Matrine inhibits the invasive properties of human osteosarcoma cells by downregulating the ERK-NF-κB pathway. Anticancer Drugs. 25:1035–1043. 2014. View Article : Google Scholar : PubMed/NCBI
17	Yang G, Yuan J and Li K: EMT transcription factors: Implication in osteosarcoma. Med Oncol. 30:6972013. View Article : Google Scholar : PubMed/NCBI
18	PosthumaDeBoer J, Witlox MA, Kaspers GJ and van Royen BJ: Molecular alterations as target for therapy in metastatic osteosarcoma: A review of literature. Clin Exp Metastasis. 28:493–503. 2011. View Article : Google Scholar : PubMed/NCBI
19	Krishnan K, Khanna C and Helman LJ: The biology of metastases in pediatric sarcomas. Cancer J. 11:306–313. 2005. View Article : Google Scholar : PubMed/NCBI
20	Harting MT and Blakely ML: Management of osteosarcoma pulmonary metastases. Semin Pediatr Surg. 15:25–29. 2006. View Article : Google Scholar : PubMed/NCBI
21	Khan JA, Tao X and Tong L: Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat Struct Mol Biol. 13:582–588. 2006. View Article : Google Scholar : PubMed/NCBI
22	Wang T, Zhang X, Bheda P, Revollo JR, Imai S and Wolberger C: Structure of Nampt/PBEF/visfatin, a mammalian NAD⁺ biosynthetic enzyme. Nat Struct Mol Biol. 13:661–662. 2006. View Article : Google Scholar : PubMed/NCBI
23	Kim SR, Bae SK, Choi KS, Park SY, Jun HO, Lee JY, Jang HO, Yun I, Yoon KH, Kim YJ, et al: Visfatin promotes angiogenesis by activation of extracellular signal-regulated kinase 1/2. Biochem Biophys Res Commun. 357:150–156. 2007. View Article : Google Scholar : PubMed/NCBI
24	Reddy PS, Umesh S, Thota B, Tandon A, Pandey P, Hegde AS, Balasubramaniam A, Chandramouli BA, Santosh V, Rao MR, et al: PBEF1/NAmPRTase/Visfatin: A potential malignant astrocytoma/glioblastoma serum marker with prognostic value. Cancer Biol Ther. 7:663–668. 2008. View Article : Google Scholar : PubMed/NCBI
25	Van Beijnum JR, Moerkerk PT, Gerbers AJ, De Bruïne AP, Arends JW, Hoogenboom HR and Hufton SE: Target validation for genomics using peptide-specific phage antibodies: A study of five gene products overexpressed in colorectal cancer. Int J Cancer. 101:118–127. 2002. View Article : Google Scholar : PubMed/NCBI
26	Patel ST, Mistry T, Brown JE, Digby JE, Adya R, Desai KM and Randeva HS: A novel role for the adipokine visfatin/pre-B cell colony-enhancing factor 1 in prostate carcinogenesis. Peptides. 31:51–57. 2010. View Article : Google Scholar
27	Nakajima TE, Yamada Y, Hamano T, Furuta K, Gotoda T, Katai H, Kato K, Hamaguchi T and Shimada Y: Adipocytokine levels in gastric cancer patients: Resistin and visfatin as biomarkers of gastric cancer. J Gastroenterol. 44:685–690. 2009. View Article : Google Scholar : PubMed/NCBI
28	Nakajima TE, Yamada Y, Hamano T, Furuta K, Matsuda T, Fujita S, Kato K, Hamaguchi T and Shimada Y: Adipocytokines as new promising markers of colorectal tumors: Adiponectin for colorectal adenoma, and resistin and visfatin for colorectal cancer. Cancer Sci. 101:1286–1291. 2010. View Article : Google Scholar : PubMed/NCBI
29	Cichon MA and Radisky DC: ROS-induced epithelial-mesen-chymal transition in mammary epithelial cells is mediated by NF-κB-dependent activation of Snail. Oncotarget. 5:2827–2838. 2014.PubMed/NCBI
30	Yang H, Zhang Y, Zhou Z, Jiang X and Shen A: Snail-1 regulates VDR signaling and inhibits 1,25(OH)-D₃ action in osteosarcoma. Eur J Pharmacol. 670:341–346. 2011. View Article : Google Scholar : PubMed/NCBI
31	Larriba MJ, Ordóñez-Morán P, Chicote I, Martín-Fernández G, Puig I, Muñoz A and Pálmer HG: Vitamin D receptor deficiency enhances Wnt/β-catenin signaling and tumor burden in colon cancer. PLoS One. 6:e235242011. View Article : Google Scholar
32	Stubbins RE, Hakeem A and Núñez NP: Using components of the vitamin D pathway to prevent and treat colon cancer. Nutr Rev. 70:721–729. 2012. View Article : Google Scholar : PubMed/NCBI
33	Nishimura A, Akeda K, Matsubara T, Kusuzaki K, Matsumine A, Masuda K, Gemba T, Uchida A and Sudo A: Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma. Cancer Gene Ther. 18:250–259. 2011. View Article : Google Scholar
34	Huber MA, Azoitei N, Baumann B, Grünert S, Sommer A, Pehamberger H, Kraut N, Beug H and Wirth T: NF-kappaB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 114:569–581. 2004. View Article : Google Scholar : PubMed/NCBI
35	Maier HJ, Schmidt-Strassburger U, Huber MA, Wiedemann EM, Beug H and Wirth T: NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells. Cancer Lett. 295:214–228. 2010. View Article : Google Scholar : PubMed/NCBI
36	Cheng ZX, Sun B, Wang SJ, Gao Y, Zhang YM, Zhou HX, Jia G, Wang YW, Kong R, Pan SH, et al: Nuclear factor-κB-dependent epithelial to mesenchymal transition induced by HIF-1α activation in pancreatic cancer cells under hypoxic conditions. PLoS One. 6:e237522011. View Article : Google Scholar