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http://dx.doi.org/10.3746/jkfn.2013.42.8.1167

Glutamine Deprivation Inhibits Invasion of Human Prostate Carcinoma LnCap Cells through Inactivation of Matrix Metalloproteinases and Modulation of Tight Junctions  

Shin, Dong Yeok (Dongnam Institute of Radiological & Medicine Sciences)
Choi, Yung Hyun (Dept. of Biochemistry, College of Oriental Medicine, Dongeui University, Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University)
Publication Information
Journal of the Korean Society of Food Science and Nutrition / v.42, no.8, 2013 , pp. 1167-1174 More about this Journal
Abstract
Cancer cells exhibit increased demand for glutamine-derived carbons to support anabolic processes. Indeed, the spectrum of glutamine-dependent tumors and the mechanisms through which glutamine supports cancer metabolism remain areas of active investigation. In the present study, we investigated the effects of glutamine deprivation on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LnCap cells. Glutamine deprivation markedly inhibited cell motility and invasiveness in a time-dependent manner. The anti-invasive activity of glutamine deprivation was associated with an increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in a time-dependent fashion by glutamine deprivation, which was correlated with a decrease in expression of their mRNA and proteins and up-regulation of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, glutamine deprivation repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Moreover, the levels of E-cadherin, a type I transmembrane glycoprotein, and snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were markedly modulated by glutamine deprivation. Taken together, these findings suggest that TJs and MMPs are critical targets of glutamine deprivation-induced anti-invasion in human prostate carcinoma LnCap cells.
Keywords
glutamine deprivation; LnCap; invasion; tight junction; matrix metalloproteinase;
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1 Woodhouse EC, Chuaqui RF, Liotta LA. 1997. General mechanisms of metastasis. Cancer 80: S1529-S1537.   DOI   ScienceOn
2 Chambers AF, Matrisian LM. 1997. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst 89: 1260-1270.   DOI   ScienceOn
3 Roeb E, Matern S. 2001. Matrix metalloproteinases: Promoters of tumor invasion and metastasis－A review with focus on gastrointestinal tumors. Z Gastroenterol 39: 807-813.   DOI   ScienceOn
4 Leber MF, Efferth T. 2009. Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34: 881-895.
5 Morin PJ. 2005. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res 65:9603-9606.   DOI   ScienceOn
6 Tagliarino C, Pink JJ, Dubyak GR, Nieminen AL, Boothman DA. 2001. Calcium is a key signaling molecule in $\beta$-lapachone-mediated cell death. J Biol Chem 276: 19150-19159.   DOI   ScienceOn
7 Kominsky SL, Argani P, Korz D, Evron E, Raman V, Garrett E, Rein A, Sauter G, Kallioniemi OP, Sukumar S. 2003. Loss of the tight junction protein claudin-7 correlates with histological grade in both ductal carcinoma in situ and invasive ductal carcinoma of the breast. Oncogene 22: 2021-2033.   DOI   ScienceOn
8 Mauro L, Bartucci M, Morelli C, Andò S, Surmacz E. 2001. IGF-I receptor-induced cell-cell adhesion of MCF-7 breast cancer cells requires the expression of junction protein ZO-1. J Biol Chem 276: 39892-39897.   DOI   ScienceOn
9 Lombard C, Saulnier J, Wallach J. 2005. Assays of matrix metalloproteinases (MMPs) activities: a review. Biochimie 87: 265-272.   DOI   ScienceOn
10 Kohrmann A, Kammerer U, Kapp M, Dietl J, Anacker J. 2009. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer 9:188.   DOI   ScienceOn
11 Gibbs DF, Warner RL, Weiss SJ, Johnson KJ, Varani J. 1999. Characterization of matrix metalloproteinases produced by rat alveolar macrophages. Am J Respir Cell Mol Biol 20: 1136-1144.   DOI   ScienceOn
12 Mook OR, Frederiks WM, Van Noorden CJ. 2004. The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta 1705: 69-89.
13 Lambert E, Dasse E, Haye B, Petitfrere E. 2004. TIMPs as multifacial proteins. Crit Rev Oncol Hematol 49: 187-198.   DOI   ScienceOn
14 Lee WJ, Hawkins RA, Wina JR, Peterson DR. 1998. Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal. Am J Physiol Cell Physiol 274:C1101-C1107.
15 DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. 2008. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7: 11-20.   DOI   ScienceOn
16 Weinberg F, Chandel NS. 2009. Mitochondrial metabolism and cancer. Ann NY Acad Sci 1177: 66-73.   DOI   ScienceOn
17 Ko YG, Kim EK, Kim T, Park H, Park HS, Choi EJ, Kim S. 2001. Glutamine-dependent antiapoptotic interaction of human glutaminyl-tRNA synthetase with apoptosis signalregulating kinase 1. J Biol Chem 276: 6030-6036.   DOI   ScienceOn
18 Wen G, Partridge MA, Li B, Hong M, Liao W, Cheng SK, Zhao Y, Calaf GM, Liu T, Zhou J, Zhang Z, Hei TK. 2011. TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells. Cancer Lett 308:23-32.   DOI   ScienceOn
19 Rosenthal DI, Trotti A. 2009. Strategies for managing radiation-induced mucositis in head and neck cancer. Semin Radiat Oncol 19: 29-34.   DOI   ScienceOn
20 Martin TA, Das T, Mansel RE, Jiang WG. 2006. Synergistic regulation of endothelial tight junctions by antioxidant (Se) and polyunsaturated lipid (GLA) via Claudin-5 modulation. J Cell Biochem 98: 1308-1319.   DOI   ScienceOn
21 Koochekpour S, Majumdar S, Azabdaftari G, Attwood K, Scioneaux R, Subramani D, Manhardt C, Lorusso GD, Willard SS, Thompson H, Shourideh M, Rezaei K, Sartor O, Mohler JL, Vessella RL. 2012. Serum glutamate levels correlate with Gleason score and glutamate blockade decreases proliferation, migration, and invasion and induces apoptosis in prostate cancer cells. Clin Cancer Res 18:5888-5901.   DOI
22 Fu YM, Yu ZX, Lin H, Fu X, Meadows GG. 2008. Selective amino acid restriction differentially affects the motility and directionality of DU145 and PC3 prostate cancer cells. Cell Physiol 217: 184-193.   DOI   ScienceOn
23 Fu YM, Yu ZX, Li YQ, Ge X, Sanchez PJ, Fu X, Meadows GG. 2003. Specific amino acid dependency regulates invasiveness and viability of androgen-independent prostate cancer cells. Nutr Cancer 45: 60-73.   DOI   ScienceOn
24 Visse R, Nagase H. 2003. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92: 827-839.   DOI   ScienceOn
25 Jiang Y, Goldberg ID, Shi YE. 2002. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21:2245-2252.   DOI   ScienceOn
26 Mignatti P, Rifkin DB. 1993. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 73: 161-195.
27 Kajita M, McClinic KN, Wade PA. 2004. Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol 24: 7559-7566.   DOI   ScienceOn
28 Van Itallie CM, Anderson JM. 2004. The molecular physiology of tight junction pores. Physiology (Bethesda) 19: 331-338.   DOI   ScienceOn
29 Boutet A, Esteban MA, Maxwell PH, Nieto MA. 2007. Reactivation of snail genes in renal fibrosis and carcinomas:a process of reversed embryogenesis? Cell Cycle 6: 638-642.   DOI
30 Mendelsohn AH, Lai CK, Shintaku IP, Fishbein MC, Brugman K, Elashoff DA, Abemayor E, Dubinett SM, St John MA. 2012. Snail as a novel marker for regional metastasis in head and neck squamous cell carcinoma. Am J Otolaryngol 33: 6-13.   DOI   ScienceOn
31 Li H, Wang H, Wang F, Gu Q, Xu X. 2011. Snail involves in the transforming growth factor $\beta$1-mediated epithelialmesenchymal transition of retinal pigment epithelial cells. PLoS One 6: e23322.   DOI
32 Hirohashi S, Kanai Y. 2003. Cell adhesion system and human cancer morphogenesis. Cancer Sci 94: 575-581.   DOI   ScienceOn
33 Hsu HP, Shan YS, Jin YT, Lai MD, Lin PW. 2010. Loss of E-cadherin and beta-catenin is correlated with poor prognosis of ampullary neoplasms. J Surg Oncol 101: 356-362.