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http://dx.doi.org/10.14348/molcells.2014.2247

mTOR Signal Transduction Pathways Contribute to TN-C FNIII A1 Overexpression by Mechanical Stress in Osteosarcoma Cells  

Zheng, Lianhe (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
Zhang, Dianzhong (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
Zhang, Yunfei (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
Wen, Yanhua (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
Wang, Yucai (Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University)
Publication Information
Molecules and Cells / v.37, no.2, 2014 , pp. 118-125 More about this Journal
Abstract
Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosarcoma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migration. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients.
Keywords
mechanical stimulation; MG-63 cells; osteosarcoma; tenascin-C; TN-C FNIIIA1;
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1 Lv, Z., Yang, D., Li, J., Hu, M., Luo, M., Zhan, X., Song, P., Liu, C., Bai, H., and Li, B. (2013). Bone morphogenetic protein 9 overexpression reduces osteosarcoma cell migration and invasion. Mol. Cells 36, 119-126.   DOI
2 Ma, X.M., and Blenis, J. (2009). Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10, 307-318.   DOI   ScienceOn
3 Midwood, K.S., and Orend, G. (2009). The role of tenascin-C in tissue injury and tumorigenesis. J. Cell Commun. Signal. 3, 287-310.   DOI
4 Midwood, K.S., Hussenet, T., Langlois, B., and Orend, G. (2011). Advances in tenascin-C biology. Cell. Mol. Life Sci. 68, 3175-3199.   DOI   ScienceOn
5 Oh, W.J., and Jacinto, E. (2011). mTOR complex 2 signaling and functions. Cell Cycle 10, 2305-2316.   DOI
6 Osborne, T., and Khanna, C. (2012). A review of the association between osteosarcoma metastasis and protein translation. J. Comp. Pathol. 146, 132-142.   DOI   ScienceOn
7 Ramos, D.M., Chen, B., Regezi, J., Zardi, L., and Pytela, R. (1998). Tenascin-C matrix assembly in oral squamous cell carcinoma. Int. J. Cancer 75, 680-687.   DOI
8 Rhee, S.H., Han, I., Lee, M.R., Cho, H.S., Oh, J.H., and Kim, H.S. (2013). Role of integrin-linked kinase in osteosarcoma progression. J. Orthopaedic. Res. 31, 1668-1675.   DOI   ScienceOn
9 Sage, E., and Bornstein, P. (1991). Extracellular proteins that modulate cell-matrix interactions. SPARC, tenascin, and thrombospondin. J. Biol. Chem. 266, 14831-14834.
10 Saito, Y., Imazeki, H., Miura, S., Yoshimura, T., Okutsu, H., Harada, Y., Ohwaki, T., Nagao, O., Kamiya, S., and Hayashi, R. (2007). A peptide derived from tenascin-C induces ${\beta}1$ integrin activation through syndecan-4. J. Biol. Chem. 282, 34929-34937.   DOI   ScienceOn
11 Tamaoki, M., Imanaka-Yoshida, K., Yokoyama, K., Nishioka, T., Inada, H., Hiroe, M., Sakakura, T., and Yoshida, T. (2005). Tenascin-C regulates recruitment of myofibroblasts during tissue repair after myocardial injury. Am. J. Pathol. 167, 71-80.   DOI   ScienceOn
12 Shimoyama, T., Hiraoka, S., Takemoto, M., Koshizaka, M., Tokuyama, H., Tokuyama, T., Watanabe, A., Fujimoto, M., Kawamura, H., and Sato, S. (2010). CCN3 inhibits neointimal hyperplasia through modulation of smooth muscle cell growth and migration. Arterioscler. Thromb. Vasc. Biol. 30, 675-682.   DOI   ScienceOn
13 Si, Y., Wang, J., Guan, J., Han, Q., and Hui, Y. (2013). Plateletderived growth factor induced alpha-smooth muscle actin expression by human retinal pigment epithelium cell. J. Ocul. Pharmacol. Ther. 29, 310-318.   DOI   ScienceOn
14 Skelly, D.T., Hennessy, E., Dansereau, M.-A., and Cunningham, C. (2013). A systematic analysis of the peripheral and CNS effects of systemic LPS, IL-1B, TNF-${\alpha}$ and IL-6 challenges in C57BL/6 mice. PLoS One 8, e69123.   DOI
15 Tucker, R.P., and Chiquet-Ehrismann, R. (2009). The regulation of tenascin expression by tissue microenvironments. Biochim. Biophys. Acta 1793, 888-892.   DOI   ScienceOn
16 Wachtel, M., and Schafer, B.W. (2010). Targets for cancer therapy in childhood sarcomas. Cancer Treat. Rev. 36, 318-327.   DOI   ScienceOn
17 Wang, Y., Man, Y., Ding, Y., Ma, B., Qiu, X., Fan, Q., Zheng, L. (2006). Mechanical strain and growth factors regulate expression of tenascin-C by OS cells additively. Oncol. Res. 20, 509-516.
18 Wu, G., Wang, J., Zhou, Z., Li, T., and Tang, F. (2013). Combined staining for immunohistochemical markers in the diagnosis of papillary thyroid carcinoma: Improvement in the sensitivity or specificity? J. Int. Med. Res. 41, 975-983.   DOI
19 Yuan, T., and Cantley, L. (2008). PI3K pathway alterations in cancer: variations on a theme. Oncogene 27, 5497-5510.   DOI   ScienceOn
20 Wang, Y., Zheng, L., Ma, B., Zhou, Y., and Fan, Q. (2010). Generation and identification of monoclonal antibodies against FNIII domain D of human tenascin-C. Hybridoma (Larchmt) 29, 13-16.   DOI   ScienceOn
21 Wullschleger, S., Loewith, R., and Hall, M.N. (2006). TOR signaling in growth and metabolism. Cell 124, 471-484.   DOI   ScienceOn
22 Murphy-Ullrich, J.E. (2001). The de-adhesive activity of matricellular proteins: is intermediate cell adhesion an adaptive state? J. Clin. Invest. 107, 785-790.   DOI   ScienceOn
23 Ehrlich, P., and Lanyon, L. (2002). Mechanical strain and bone cell function: a review. Osteoporosis Int. 13, 688-700.   DOI   ScienceOn
24 Chung, C.Y., and Erickson, H. (1994). Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C. J. Cell Biol. 126, 539-548.   DOI
25 Andrianarivo, A.G., Robinson, J.A., Mann, K.G., and Tracy, R.P. (1992). Growth on type I collagen promotes expression of the osteoblastic phenotype in human osteosarcoma MG-63 cells. J. Cell. Physiol. 153, 256-265.   DOI
26 Bielack, S., Carrle, D., Casali, P.G., and Group, O.b.o.t.E.G.W. (2009). Osteosarcoma: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann. Oncol. 20, iv137-iv139.   DOI
27 Lelievre, S., Bisseil, M.J., and Pujuguet, P. (2000). Cell nucleus in context. Crit. Rev. Eukaryot. Gene Exp. 10, 30-37.
28 Feng, X., Zhang, Y., Xu, R., Xie, X., Tao, L., Gao, H., Gao, Y., He, Z., and Wang, H. (2010). Lipopolysaccharide up-regulates the expression of $Fc{\alpha}/{\mu}$ receptor and promotes the binding of oxidized low-density lipoprotein and its IgM antibody complex to activated human macrophages. Atherosclerosis 208, 396-405.   DOI   ScienceOn
29 Gill, J., Ahluwalia, M.K., Geller, D., and Gorlick, R. (2012). New targets and approaches in osteosarcoma. Pharmacol. Ther. 137, 89-99.
30 Hirata, E., Arakawa, Y., Shirahata, M., Yamaguchi, M., Kishi, Y., Okada, T., Takahashi, J.A., Matsuda, M., and Hashimoto, N. (2009). Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue. Cancer Sci. 100, 1451-1459.   DOI   ScienceOn
31 Jahkola, T., Toivonen, T., Virtanen, I., von Smitten, K., Nordling, S., von Boguslawski, K., Haglund, C., Nevanlinna, H., and Blomqvist, C. (1998). Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence. Br. J. Cancer 78, 1507.   DOI
32 Leins, A., Riva, P., Lindstedt, R., Davidoff, M.S., Mehraein, P., and Weis, S. (2003). Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer 98, 2430-2439.   DOI   ScienceOn
33 Li, R., Maminishkis, A., Wang, F.E., and Miller, S.S. (2007). PDGFC and-D induced proliferation/migration of human RPE is abolished by inflammatory cytokines. Invest. Ophthalmol. Vis. Sci. 48, 5722-5732.   DOI   ScienceOn
34 Zhang, Y., and Zheng, X.S. (2012). mTOR-independent 4E-BP1 phosphorylation is associated with cancer resistance to mTOR kinase inhibitors. Cell Cycle 11, 594-603.   DOI
35 Alves, T.R., da Fonseca, A.C.C., Nunes, S.S., da Silva, A.O., Dubois, L.G.F., Faria, J., Kahn, S.A., Viana, N.B., Marcondes, J., Legrand, C., et al. (2011). Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells. Exp. Cell Res. 317, 2073-2085.   DOI   ScienceOn
36 Jiang, L., Wei, X., Yi, D., Xu, P., Liu, H., Chang, Q., Yang, S., Li, Z., Gao, H., and Hao, G. (2008). Synergistic effects of cyclic strain and Th1-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells. Clin. Exp. Immunol. 155, 216-223.
37 Pazzaglia, L., Conti, A., Chiechi, A., Novello, C., Magagnoli, G., Astolfi, A., Pession, A., Krenacs, T., Alberghini, M., and Picci, P. (2010). Differential gene expression in classic giant cell tumours of bone: tenascin C as biological risk factor for local relapses and metastases. Histopathology 57, 59-72.   DOI   ScienceOn
38 Tucker, R., Drabikowski, K., Hess, J., Ferralli, J., Chiquet-Ehrismann, R., and Adams, J. (2006). Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage. BMC Evol. Biol. 6, 60.   DOI   ScienceOn