Abstract
Molecular mechanisms underlying thyroid tumorigenesis and identifying new therapeutic targets are still under investigation. We aim to investigate the role of CD146 and latexin (Lxn) and examine whether they have any clinical significance in thyroid cancer. Human thyroid papillary (PTC), follicular (FTC), anaplastic (ATC) cancer cells, and other control cells were used in this study. Western blot, cell proliferation, invasion assay, and shRNA were applied to study the expression levels and functional significances of CD146 and Lxn in thyroid cells. The protein expression was evaluated by immunohistochemistry using human tissue microarray (TMA) slides. Multivariate analysis was used to examine whether these proteins have any clinical significance in patients with thyroid cancer. The protein expressions of CD146 and Lxn were detected in most thyroid cancer cell lines when compared with normal cells. Notably, knockdown of CD146 reduced the migration and invasion in K1 (PTC) and OCUT-1 (ATC) cells. TMAs showed more immunoreactivity against CD146 and Lxn in PTC cores compared with FTC, ATC, and normal tissues. A positive correlation was established between CD146 and both Lxn (r = 0.421, p = 0.045) and age (r = 0.566, p = 0.012); however, it showed a negative correlation with tumor stage (r = −0.231, p = 0.010). In conclusion, CD146 and Lxn increased tumor migration and invasion in vitro and showed a high expression in PTC compared to those in ATC and normal human tissues demonstrating their role in early stage of thyroid tumorigenesis. CD146 was positively correlated with age, but negatively correlated with tumor stage.
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Hundahl SA, Fleming ID, Fremgen AM, Menck HR (1998) A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see comments]. Cancer 83:2638–2648
Altekruse SF KC, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, et al (eds). SEER Cancer Statistics Review, 1975–2007, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2007/, based on November 2009 SEER data submission, posted to the SEER web site, 2010
Brzezianska E, Pastuszak-Lewandoska D (2011) A minireview: the role of MAPK/ERK and PI3 K/Akt pathways in thyroid follicular cell-derived neoplasm. Front Biosci 16:422–439
Makita N, Iiri T (2013) Tyrosine kinase inhibitor-induced thyroid disorders: a review and hypothesis. Thyroid 23:151–159
Johnson JP, Rummel MM, Rothbacher U, Sers C (1996) MUC18: a cell adhesion molecule with a potential role in tumor growth and tumor cell dissemination. Curr Top Microbiol Immunol 213(Pt 1):95–105
Anfosso F, Bardin N, Vivier E, Sabatier F, Sampol J, Dignat-George F (2001) Outside-in signaling pathway linked to CD146 engagement in human endothelial cells. J Biol Chem 276:1564–1569
Blann AD, Woywodt A, Bertolini F, Bull TM, Buyon JP, Clancy RM, Haubitz M, Hebbel RP, Lip GY, Mancuso P, Sampol J, Solovey A, Dignat-George F (2005) Circulating endothelial cellsBiomarker of vascular disease. Thromb Haemost 93:228–235
Khan SS, Solomon MA, McCoy JP Jr (2005) Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 64:1–8
Shih LM, Hsu MY, Palazzo JP, Herlyn M (1997) The cell–cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. Am J Pathol 151:745–751
Imbert AM, Garulli C, Choquet E, Koubi M, Aurrand-Lions M, Chabannon C (2012) CD146 expression in human breast cancer cell lines induces phenotypic and functional changes observed in epithelial to mesenchymal transition. PLoS ONE 7:e43752
Zeng Q, Li W, Lu D, Wu Z, Duan H, Luo Y, Feng J, Yang D, Fu L, Yan X (2012) CD146, an epithelial-mesenchymal transition inducer, is associated with triple-negative breast cancer. Proc Natl Acad Sci USA 109:1127–1132
Arimatsu Y (1994) Latexin: a molecular marker for regional specification in the neocortex. Neurosci Res 20:131–135
Hatanaka Y, Uratani Y, Takiguchi-Hayashi K, Omori A, Sato K, Miyamoto M, Arimatsu Y (1994) Intracortical regionality represented by specific transcription for a novel protein, latexin. Eur J Neurosci 6:973–982
Liu Q, Yu L, Gao J, Fu Q, Zhang J, Zhang P, Chen J, Zhao S (2000) Cloning, tissue expression pattern and genomic organization of latexin, a human homologue of rat carboxypeptidase A inhibitor. Mol Biol Rep 27:241–246
Pallares I, Bonet R, Garcia-Castellanos R, Ventura S, Aviles FX, Vendrell J, Gomis-Ruth FX (2005) Structure of human carboxypeptidase A4 with its endogenous protein inhibitor, latexin. Proc Natl Acad Sci USA 102:3978–3983
Callahan G, Hartmann, L, Smith, D (1999) Characterization of a carboxypeptidase—A inhibitor identified by DD-PCR in primary ovarian tumors and cell lines. Faseb J f 637
Van Zant G, Liang Y (2009) Natural genetic diversity as a means to uncover stem cell regulatory pathways. Ann N Y Acad Sci 1176:170–177
Liang Y, Van Zant G (2008) Aging stem cells, latexin, and longevity. Exp Cell Res 314:1962–1972
Nada AS, Hawas AM, Amin Nel D, Elnashar MM, Abd Elmageed ZY (2012) Radioprotective effect of Curcuma longa extract on gamma-irradiation-induced oxidative stress in rats. Can J Physiol Pharmacol 90:415–423
McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS Sr (1985) Estrogen receptor analyses—correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109:716–721
Liu D, Hou P, Liu Z, Wu G, Xing M (2009) Genetic alterations in the phosphoinositide 3-kinase/Akt signaling pathway confer sensitivity of thyroid cancer cells to therapeutic targeting of Akt and mammalian target of rapamycin. Cancer Res 69:7311–7319
Yan X, Lin Y, Yang D, Shen Y, Yuan M, Zhang Z, Li P, Xia H, Li L, Luo D, Liu Q, Mann K, Bader BL (2003) A novel anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis and tumor growth. Blood 102:184–191
Vleminckx KL, Deman JJ, Bruyneel EA, Vandenbossche GM, Keirsebilck AA, Mareel MM, van Roy FM (1994) Enlarged cell-associated proteoglycans abolish E-cadherin functionality in invasive tumor cells. Cancer Res 54:873–877
Hedrick L, Cho KR, Boyd J, Risinger J, Vogelstein B (1992) DCC: a tumor suppressor gene expressed on the cell surface. Cold Spring Harb Symp Quant Biol 57:345–351
Lehmann JM, Riethmuller G, Johnson JP (1989) MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci USA 86:9891–9895
Vainio O, Dunon D, Aissi F, Dangy JP, McNagny KM, Imhof BA (1996) HEMCAM, an adhesion molecule expressed by c-kit + hemopoietic progenitors. J Cell Biol 135:1655–1668
Tanaka H, Matsui T, Agata A, Tomura M, Kubota I, McFarland KC, Kohr B, Lee A, Phillips HS, Shelton DL (1991) Molecular cloning and expression of a novel adhesion molecule, SC1. Neuron 7:535–545
Pourquie O, Corbel C, Le Caer JP, Rossier J, Le Douarin NM (1992) BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. Proc Natl Acad Sci USA 89:5261–5265
Burns FR, von Kannen S, Guy L, Raper JA, Kamholz J, Chang S (1991) DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. Neuron 7:209–220
Bu P, Zhuang J, Feng J, Yang D, Shen X, Yan X (2007) Visualization of CD146 dimerization and its regulation in living cells. Biochim Biophys Acta 1773:513–520
Sorrentino A, Ferracin M, Castelli G, Biffoni M, Tomaselli G, Baiocchi M, Fatica A, Negrini M, Peschle C, Valtieri M (2008) Isolation and characterization of CD146 + multipotent mesenchymal stromal cells. Exp Hematol 36:1035–1046
Covas DT, Panepucci RA, Fontes AM, Silva WA Jr, Orellana MD, Freitas MC, Neder L, Santos AR, Peres LC, Jamur MC, Zago MA (2008) Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146 + perivascular cells and fibroblasts. Exp Hematol 36:642–654
Corticchiato O, Cajot JF, Abrahamson M, Chan SJ, Keppler D, Sordat B (1992) Cystatin C and cathepsin B in human colon carcinoma: expression by cell lines and matrix degradation. Int J Cancer 52:645–652
Konduri SD, Yanamandra N, Siddique K, Joseph A, Dinh DH, Olivero WC, Gujrati M, Kouraklis G, Swaroop A, Kyritsis AP, Rao JS (2002) Modulation of cystatin C expression impairs the invasive and tumorigenic potential of human glioblastoma cells. Oncogene 21:8705–8712
Wai Wong C, Dye DE, Coombe DR (2012) The role of immunoglobulin superfamily cell adhesion molecules in cancer metastasis. Int J Cell Biol 2012:340296
Jouve N, Despoix N, Espeli M, Gauthier L, Cypowyj S, Fallague K, Schiff C, Dignat-George F, Vely F, Leroyer AS (2013) The involvement of CD146 and its novel ligand galectin-1 in apoptotic regulation of endothelial cells. J Biol Chem 288:2571–2579
Leitzmann MF, Rohrmann S (2012) Risk factors for the onset of prostatic cancer: age, location, and behavioral correlates. Clin Epidemiol 4:1–11
Wolf AM, Wender RC, Etzioni RB, Thompson IM, D’Amico AV, Volk RJ, Brooks DD, Dash C, Guessous I, Andrews K, DeSantis C, Smith RA (2010) American cancer society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 60:70–98
Cho E, Rosner BA, Feskanich D, Colditz GA (2005) Risk factors and individual probabilities of melanoma for whites. J Clin Oncol 23:2669–2675
Dean DS, Hay ID (2000) Prognostic indicators in differentiated thyroid carcinoma. Cancer Control 7:229–239
Mazzaferri EL, Kloos RT (2001) Clinical review 128: current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 86:1447–1463
Ma X, Liu J, Wu J, Yan X, Wu P, Liu Y, Li S, Tian Y, Cao Y, Chen G, Meng L, Xu G, Wang S, Lu Y, Ma D, Zhou J (2010) Synergistic killing effect between vorinostat and target of CD146 in malignant cells. Clin Cancer Res 16:5165–5176
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Abd Elmageed, Z.Y., Moroz, K. & Kandil, E. Clinical significance of CD146 and latexin during different stages of thyroid cancer. Mol Cell Biochem 381, 95–103 (2013). https://doi.org/10.1007/s11010-013-1691-x
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DOI: https://doi.org/10.1007/s11010-013-1691-x