The role of mechano-growth factor E peptide in the regulation of osteosarcoma

Shang,Jin; Fan,Xin; Liu,Huan

doi:10.3892/ol.2015.3339

The role of mechano-growth factor E peptide in the regulation of osteosarcoma

Authors:
- Jin Shang
- Xin Fan
- Huan Liu
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Affiliations: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Published online on: June 9, 2015 https://doi.org/10.3892/ol.2015.3339
Pages: 697-704
Copyright: © Shang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is one of the most common bone tumors, and exhibits a high degree of malignancy. Gene therapy is a novel approach to its treatment, however, specific target genes are required to enable effective use of this therapy. In order to investigate the effects of the mechano‑growth factor E (MGF‑E) peptide, which is derived from the IGF‑I alternative splicing isoform, on the regulation of the development of osteosarcoma, the expression of MGF was detected in osteosarcoma cell lines with different degrees of malignancy. Concomitantly, exogenous MGF‑E peptide was used to stimulate these osteosarcoma cell lines. The results demonstrated that MGF was overexpressed in malignant osteosarcoma cells, while it was not expressed in the least malignant osteosarcoma cells. Furthermore, MGF‑E treatment altered the cell cycle distribution, and promoted the proliferation, migration and invasion of osteosarcoma cells. The possible mechanisms underlying these effects were detected by quantitative polymerase chain reaction and western blotting. Based on these results, it was hypothesized that MGF may be a suitable biomarker for malignant osteosarcoma phenotypes.

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1	Marulanda GA, Henderson ER, Johnson DA, Letson GD and Cheong D: Orthopedic surgery options for the treatment of primary osteosarcoma. Cancer Control. 15:13–20. 2008.PubMed/NCBI
2	Vander Griend RA: Osteosarcoma and its variants. Orthop Clin North Am. 27:575–581. 1996.PubMed/NCBI
3	Kim SY and Helman LJ: Strategies to explore new approaches in the investigation and treatment of osteosarcoma. Cancer Treat Res. 152:517–528. 2009. View Article : Google Scholar : PubMed/NCBI
4	Nardin A, Lefebvre ML, Labroquère K, Faure O and Abastado JP: Liposomal muramyl tripeptide phosphatidylethanolamine: Targeting and activating macrophages for adjuvant treatment of osteosarcoma. Curr Cancer Drug Targets. 6:123–133. 2006. View Article : Google Scholar : PubMed/NCBI
5	Xie XK, Yang DS, Ye ZM and Tao HM: Enhancement effect of adenovirus-mediated antisense c-myc and caffeine on the cytotoxicity of cisplatin in osteosarcoma cell lines. Chemotherapy. 55:433–440. 2009. View Article : Google Scholar : PubMed/NCBI
6	Oosterhoff D, Witlox MA, van Beusechem VW, Haisma HJ, Schaap GR, Bras J, Kruyt FA, Molenaar B, Boven E, Wuisman PI, et al: Gene-directed enzyme prodrug therapy for osteosarcoma: Sensitization to CPT-11 in vitro and in vivo by adenoviral delivery of a gene encoding secreted carboxylesterase-2. Mol Cancer Ther. 2:765–771. 2003.PubMed/NCBI
7	Shavlakadze T, Winn N, Rosenthal N and Grounds MD: Reconciling data from transgenic mice that overexpress IGF-I specifically in skeletal muscle. Growth Horm IGF Res. 15:4–18. 2005. View Article : Google Scholar : PubMed/NCBI
8	Yang S, Alnaqeeb M, Simpson H and Goldspink G: Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch. J Muscle Res Cell Motil. 17:487–495. 1996. View Article : Google Scholar : PubMed/NCBI
9	Goldspink G: Mechanical signals, IGF-I gene splicing, and muscle adaptation. Physiology (Bethesda). 20:232–238. 2005. View Article : Google Scholar : PubMed/NCBI
10	Carro E, Trejo JL, Núñez A and Torres-Aleman I: Brain repair and neuroprotection by serum insulin-like growth factor I. Mol Neurobiol. 27:153–162. 2003. View Article : Google Scholar : PubMed/NCBI
11	Tang LL, Xian CY and Wang YL: The MGF expression of osteoblasts in response to mechanical overload. Arch Oral Biol. 51:1080–1085. 2006. View Article : Google Scholar : PubMed/NCBI
12	Mills P, Lafrenière JF, Benabdallah BF, El Fahime M and Tremblay JP: A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor. Exp Cell Res. 313:527–537. 2007. View Article : Google Scholar : PubMed/NCBI
13	Collins JM, Goldspink PH and Russell B: Migration and proliferation of human mesenchymal stem cells is stimulated by different regions of the mechano-growth factor prohormone. J Mol Cell Cardiol. 49:1042–1045. 2010. View Article : Google Scholar : PubMed/NCBI
14	Matheny RW Jr, Nindl BC and Adamo ML: Minireview: Mechano-growth factor: A putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 151:865–875. 2010. View Article : Google Scholar : PubMed/NCBI
15	Kuo YH and Chen TT: Novel activities of pro-IGF-I E peptides: Regulation of morphological differentiation and anchorage-independent growth in human neuroblastoma cells. Exp Cell Res. 280:75–89. 2002. View Article : Google Scholar : PubMed/NCBI
16	Armakolas A, Philippou A, Panteleakou Z, Nezos A, Sourla A, Petraki C and Koutsilieris M: Preferential expression of IGF-1Ec (MGF) transcript in cancerous tissues of human prostate: Evidence for a novel and autonomous growth factor activity of MGF E peptide in human prostate cancer cells. Prostate. 70:1233–1242. 2010. View Article : Google Scholar : PubMed/NCBI
17	Philippou A, Armakolas A, Panteleakou Z, Pissimissis N, Nezos A, Theos A, Kaparelou M, Armakolas N, Pneumaticos SG and Koutsilieris M: IGF1Ec expression in MG-63 human osteoblast-like osteosarcoma cells. Anticancer Res. 31:4259–4265. 2011.PubMed/NCBI
18	Ates K, Yang SY, Orrell RW, Sinanan AC, Simons P, Solomon A, Beech S, Goldspink G and Lewis MP: The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle. FEBS Lett. 581:2727–2732. 2007. View Article : Google Scholar : PubMed/NCBI
19	Quesada A, Micevych P and Handforth A: C-terminal mechano growth factor protects dopamine neurons: A novel peptide that induces heme oxygenase-1. Exp Neurol. 220:255–266. 2009. View Article : Google Scholar : PubMed/NCBI
20	Wang C, Li Z, Fu M, Bouras T and Pestell RG: Signal transduction mediated by cyclin D1: From mitogens to cell proliferation: A molecular target with therapeutic potential. Cancer Treat Res. 119:217–237. 2004. View Article : Google Scholar : PubMed/NCBI
21	Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI
22	Harry LE and Paleolog EM: From the cradle to the clinic: VEGF in developmental, physiological, and pathological angiogenesis. Birth Defects Res C Embryo Today. 69:363–374. 2003. View Article : Google Scholar : PubMed/NCBI
23	Zhao S, Ma W, Zhang M, Tang D, Shi Q, Xu S, Zhang X, Liu Y, Song Y, Liu L and Zhang Q: High expression of CD147 and MMP-9 is correlated with poor prognosis of triple-negative breast cancer (TNBC) patients. Med Oncol. 30:3352013. View Article : Google Scholar : PubMed/NCBI
24	Gou X, Chen H, Jin F, Wu W, Li Y, Long J, Gong X, Luo M, Bi T, Li Z and He Q: Expressions of CD147, MMP-2 and MMP-9 in laryngeal carcinoma and its correlation with poor prognosis. Pathol Oncol Res. 20:475–481. 2014. View Article : Google Scholar : PubMed/NCBI
25	Daft PG, Yuan K, Warram JM, et al: Alpha-CaMKII plays a critical role in determining the aggressive behavior of human osteosarcoma. Mol Cancer Res. 11:349–359. 2013. View Article : Google Scholar : PubMed/NCBI
26	Crane JL and Cao X: Function of matrix IGF-1 in coupling bone resorption and formation. J Mol Med. 92:107–115. 2014. View Article : Google Scholar : PubMed/NCBI
27	Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G and Winslet M: Biology of insulin-like growth factor binding protein-4 and its role in cancer (review). Int J Oncol. 28:1317–1325. 2006.PubMed/NCBI
28	van Golen CM, Schwab TS, Kim B, Soules ME, Su Oh S, Fung K, van Golen KL and Feldman EL: Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res. 66:6570–6578. 2006. View Article : Google Scholar : PubMed/NCBI
29	Matheny RW Jr, Nindl BC and Adamo ML: Minireview: Mechano-growth factor: A putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 151:865–875. 2010. View Article : Google Scholar : PubMed/NCBI
30	Tang ZY, Liu Y, Liu LX, Ding XY, Zhang H and Fang LQ: RNAi-mediated MMP-9 silencing inhibits mouse melanoma cell invasion and migration in vitro and in vivo. Cell Biol Int. 37:849–854. 2013. View Article : Google Scholar : PubMed/NCBI
31	Li Z, Ren Y, Wu QC, Lin SX, Liang YJ and Liang HZ: Macrophage migration inhibitory factor enhances neoplastic cell invasion by inducing the expression of matrix metalloproteinase 9 and interleukin-8 in nasopharyngeal carcinoma cell lines. Chin Med J (Engl). 117:107–114. 2004.PubMed/NCBI
32	Yu W, Liu J, Xiong X, Ai Y and Wang H: Expression of MMP9 and CD147 in invasive squamous cell carcinoma of the uterine cervix and their implication. Pathol Res Pract. 205:709–715. 2009. View Article : Google Scholar : PubMed/NCBI