메뉴 건너뛰기




Volumn 7, Issue 9, 2012, Pages

Mac-2 Binding Protein Is a Novel E-Selectin Ligand Expressed by Breast Cancer Cells

Author keywords

[No Author keywords available]

Indexed keywords

ANTIGEN; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; HECA 452 ANTIGEN; MAC 2 BINDING PROTEIN; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG;

EID: 84866115129     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0044529     Document Type: Article
Times cited : (55)

References (58)
  • 4
    • 33744920615 scopus 로고    scopus 로고
    • HCELL is the major E-and L-selectin ligand expressed on LS174T colon carcinoma cells
    • Burdick MM, Chu JT, Godar S, Sackstein R, (2006) HCELL is the major E-and L-selectin ligand expressed on LS174T colon carcinoma cells. Journal of Biological Chemistry 281: 13899-13905.
    • (2006) Journal of Biological Chemistry , vol.281 , pp. 13899-13905
    • Burdick, M.M.1    Chu, J.T.2    Godar, S.3    Sackstein, R.4
  • 7
    • 0027137487 scopus 로고
    • Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions
    • Giavazzi R, Foppolo M, Dossi R, Remuzzi A, (1993) Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions. Journal of Clinical Investigation 92: 3038-3044.
    • (1993) Journal of Clinical Investigation , vol.92 , pp. 3038-3044
    • Giavazzi, R.1    Foppolo, M.2    Dossi, R.3    Remuzzi, A.4
  • 8
    • 0028839989 scopus 로고
    • E-Selectin mediated dynamic interactions of breast cancer and colon cancer cells with endothelial cell monolayers
    • Tozeren A, Kleinman HK, Grant DS, Morales D, Mercurio AM, et al. (1995) E-Selectin mediated dynamic interactions of breast cancer and colon cancer cells with endothelial cell monolayers. International Journal of Cancer 60: 426-431.
    • (1995) International Journal of Cancer , vol.60 , pp. 426-431
    • Tozeren, A.1    Kleinman, H.K.2    Grant, D.S.3    Morales, D.4    Mercurio, A.M.5
  • 9
    • 80054023220 scopus 로고    scopus 로고
    • Hematogenous metastasis: roles of CD44v and alternative sialofucosylated selectin ligands
    • Konstantopoulos K, Thomas SN, (2011) Hematogenous metastasis: roles of CD44v and alternative sialofucosylated selectin ligands. Advances in Experimental Medicine and Biology 705: 601-619.
    • (2011) Advances in Experimental Medicine and Biology , vol.705 , pp. 601-619
    • Konstantopoulos, K.1    Thomas, S.N.2
  • 10
    • 84863272678 scopus 로고    scopus 로고
    • Mucin 16 is a functional selectin ligand on pancreatic cancer cells
    • Chen SH, Dallas MR, Balzer EM, Konstantopoulos K, (2012) Mucin 16 is a functional selectin ligand on pancreatic cancer cells. FASEB Journal 26: 1349-1359.
    • (2012) FASEB Journal , vol.26 , pp. 1349-1359
    • Chen, S.H.1    Dallas, M.R.2    Balzer, E.M.3    Konstantopoulos, K.4
  • 11
    • 77952687197 scopus 로고    scopus 로고
    • E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling
    • Yago T, Shao B, Miner JJ, Yao L, Klopocki AG, et al. (2010) E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling. Blood 116: 485-494.
    • (2010) Blood , vol.116 , pp. 485-494
    • Yago, T.1    Shao, B.2    Miner, J.J.3    Yao, L.4    Klopocki, A.G.5
  • 12
    • 33749485053 scopus 로고    scopus 로고
    • Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases
    • Tremblay PL, Auger FA, Huot J, (2006) Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases. Oncogene 25: 6563-6573.
    • (2006) Oncogene , vol.25 , pp. 6563-6573
    • Tremblay, P.L.1    Auger, F.A.2    Huot, J.3
  • 13
    • 44449114208 scopus 로고    scopus 로고
    • Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis
    • Gout S, Tremblay PL, Huot J, (2008) Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis. Clinical & Experimental Metastasis 25: 335-344.
    • (2008) Clinical & Experimental Metastasis , vol.25 , pp. 335-344
    • Gout, S.1    Tremblay, P.L.2    Huot, J.3
  • 14
    • 0030795980 scopus 로고    scopus 로고
    • Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin
    • Mannori G, Santoro D, Carter L, Corless C, Nelson RM, et al. (1997) Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. American Journal of Pathology 151: 233-243.
    • (1997) American Journal of Pathology , vol.151 , pp. 233-243
    • Mannori, G.1    Santoro, D.2    Carter, L.3    Corless, C.4    Nelson, R.M.5
  • 18
    • 65249108221 scopus 로고    scopus 로고
    • Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells
    • Thomas SN, Schnaar RL, Konstantopoulos K, (2009) Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells. American Journal of Physiology: Cell Physiology 296: C505-C513.
    • (2009) American Journal of Physiology: Cell Physiology , vol.296
    • Thomas, S.N.1    Schnaar, R.L.2    Konstantopoulos, K.3
  • 19
    • 47049127247 scopus 로고    scopus 로고
    • Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E-and L-selectin in shear flow
    • Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K, (2008) Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E-and L-selectin in shear flow. Journal of Biological Chemistry 283: 15647-15655.
    • (2008) Journal of Biological Chemistry , vol.283 , pp. 15647-15655
    • Thomas, S.N.1    Zhu, F.2    Schnaar, R.L.3    Alves, C.S.4    Konstantopoulos, K.5
  • 20
    • 0034606221 scopus 로고    scopus 로고
    • P-Selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration
    • Hirata T, Merrill-Skoloff G, Aab M, Yang J, Furie BC, et al. (2000) P-Selectin glycoprotein ligand 1 (PSGL-1) is a physiological ligand for E-selectin in mediating T helper 1 lymphocyte migration. Journal of Experimental Medicine 192: 1669-1676.
    • (2000) Journal of Experimental Medicine , vol.192 , pp. 1669-1676
    • Hirata, T.1    Merrill-Skoloff, G.2    Aab, M.3    Yang, J.4    Furie, B.C.5
  • 21
    • 3442889380 scopus 로고    scopus 로고
    • Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin
    • Dimitroff CJ, Lechpammer M, Long-Woodward D, Kutok JL, (2004) Rolling of human bone-metastatic prostate tumor cells on human bone marrow endothelium under shear flow is mediated by E-selectin. Cancer research 64: 5261-5269.
    • (2004) Cancer Research , vol.64 , pp. 5261-5269
    • Dimitroff, C.J.1    Lechpammer, M.2    Long-Woodward, D.3    Kutok, J.L.4
  • 24
    • 0012289880 scopus 로고    scopus 로고
    • Adhesion of human breast cancer cells to vascular endothelium mediated by Sialyl Lewis x/E-selectin
    • Narita T, Kawakami-Kimura N, Matsuura N, Funahashi H, Kannagi R, (1996) Adhesion of human breast cancer cells to vascular endothelium mediated by Sialyl Lewis x/E-selectin. Breast Cancer 3: 19.
    • (1996) Breast Cancer , vol.3 , pp. 19
    • Narita, T.1    Kawakami-Kimura, N.2    Matsuura, N.3    Funahashi, H.4    Kannagi, R.5
  • 25
    • 79952176839 scopus 로고    scopus 로고
    • Direct measurements on CD24-mediated rolling of human breast cancer MCF-7 cells on E-selectin
    • Myung JH, Gajjar KA, Pearson RM, Launiere CA, Eddington DT, et al. (2011) Direct measurements on CD24-mediated rolling of human breast cancer MCF-7 cells on E-selectin. Analytical Chemistry 83: 1078-1083.
    • (2011) Analytical Chemistry , vol.83 , pp. 1078-1083
    • Myung, J.H.1    Gajjar, K.A.2    Pearson, R.M.3    Launiere, C.A.4    Eddington, D.T.5
  • 26
    • 46649085669 scopus 로고    scopus 로고
    • CD44v4 is a major E-selectin ligand that mediates breast cancer cell transendothelial migration
    • Zen K, Liu DQ, Guo YL, Wang C, Shan J, et al. (2008) CD44v4 is a major E-selectin ligand that mediates breast cancer cell transendothelial migration. PLoS ONE 3: e1826.
    • (2008) PLoS ONE , vol.3
    • Zen, K.1    Liu, D.Q.2    Guo, Y.L.3    Wang, C.4    Shan, J.5
  • 27
    • 84255199499 scopus 로고    scopus 로고
    • Selectin ligand sialyl-Lewis x antigen drives metastasis of hormone-dependent breast cancers
    • Julien S, Ivetic A, Grigoriadis A, QiZe D, Burford B, et al. (2011) Selectin ligand sialyl-Lewis x antigen drives metastasis of hormone-dependent breast cancers. Cancer Research 71: 7683-7693.
    • (2011) Cancer Research , vol.71 , pp. 7683-7693
    • Julien, S.1    Ivetic, A.2    Grigoriadis, A.3    QiZe, D.4    Burford, B.5
  • 28
    • 0032536822 scopus 로고    scopus 로고
    • Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta 1 integrins, collagens and fibronectin
    • Sasaki T, Brakebusch C, Engel J, Timpl R, (1998) Mac-2 binding protein is a cell-adhesive protein of the extracellular matrix which self-assembles into ring-like structures and binds beta 1 integrins, collagens and fibronectin. The EMBO Journal 17: 1606-1613.
    • (1998) The EMBO Journal , vol.17 , pp. 1606-1613
    • Sasaki, T.1    Brakebusch, C.2    Engel, J.3    Timpl, R.4
  • 30
    • 0029759376 scopus 로고    scopus 로고
    • Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion
    • Inohara H, Akahani S, Koths K, Raz A, (1996) Interactions between galectin-3 and Mac-2-binding protein mediate cell-cell adhesion. Cancer research 56: 4530-4534.
    • (1996) Cancer Research , vol.56 , pp. 4530-4534
    • Inohara, H.1    Akahani, S.2    Koths, K.3    Raz, A.4
  • 31
    • 58249091144 scopus 로고    scopus 로고
    • High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies
    • Tinari N, Lattanzio R, Querzoli P, Natoli C, Grassadonia A, et al. (2009) High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies. International Journal of Cancer 124: 333-338.
    • (2009) International Journal of Cancer , vol.124 , pp. 333-338
    • Tinari, N.1    Lattanzio, R.2    Querzoli, P.3    Natoli, C.4    Grassadonia, A.5
  • 32
    • 0035863454 scopus 로고    scopus 로고
    • Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation
    • Tinari N, Kuwabara I, Huflejt ME, Shen PF, Iacobelli S, et al. (2001) Glycoprotein 90K/MAC-2BP interacts with galectin-1 and mediates galectin-1-induced cell aggregation. International Journal of Cancer 91: 167-172.
    • (2001) International Journal of Cancer , vol.91 , pp. 167-172
    • Tinari, N.1    Kuwabara, I.2    Huflejt, M.E.3    Shen, P.F.4    Iacobelli, S.5
  • 33
    • 33749514807 scopus 로고    scopus 로고
    • Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death
    • Hernandez JD, Nguyen JT, He J, Wang W, Ardman B, et al. (2006) Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death. Journal of Immunology 177: 5328-5336.
    • (2006) Journal of Immunology , vol.177 , pp. 5328-5336
    • Hernandez, J.D.1    Nguyen, J.T.2    He, J.3    Wang, W.4    Ardman, B.5
  • 35
    • 22444451389 scopus 로고    scopus 로고
    • PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow
    • Zou X, Patil S, Vivek R, Dagia N, Smith L, et al. (2005) PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow. American Journal of Physiology- Cell Physiology 289: C415.
    • (2005) American Journal of Physiology- Cell Physiology , vol.289
    • Zou, X.1    Patil, S.2    Vivek, R.3    Dagia, N.4    Smith, L.5
  • 36
    • 0027402750 scopus 로고
    • Purification and characterization of a 90 kDa protein released from human tumors and tumor cell lines
    • Iacobelli S, Bucci I, D'Egidio M, Giuliani C, Natoli C, et al. (1993) Purification and characterization of a 90 kDa protein released from human tumors and tumor cell lines. FEBS Letters 319: 59-65.
    • (1993) FEBS Letters , vol.319 , pp. 59-65
    • Iacobelli, S.1    Bucci, I.2    D'Egidio, M.3    Giuliani, C.4    Natoli, C.5
  • 37
    • 77950682551 scopus 로고    scopus 로고
    • Identification of Mac-2-binding protein as a putative marker of neuroendocrine tumors from the analysis of cell line secretomes
    • Srirajaskanthan R, Caplin ME, Waugh MG, Watkins J, Meyer T, et al. (2010) Identification of Mac-2-binding protein as a putative marker of neuroendocrine tumors from the analysis of cell line secretomes. Mol Cell Proteomics 9: 656-666.
    • (2010) Mol Cell Proteomics , vol.9 , pp. 656-666
    • Srirajaskanthan, R.1    Caplin, M.E.2    Waugh, M.G.3    Watkins, J.4    Meyer, T.5
  • 38
    • 0032479875 scopus 로고    scopus 로고
    • Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1
    • Mazo IB, Gutierrez-Ramos JC, Frenette PS, Hynes RO, Wagner DD, et al. (1998) Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. Journal of Experimental Medical Sciences 188: 465-474.
    • (1998) Journal of Experimental Medical Sciences , vol.188 , pp. 465-474
    • Mazo, I.B.1    Gutierrez-Ramos, J.C.2    Frenette, P.S.3    Hynes, R.O.4    Wagner, D.D.5
  • 39
    • 48749115804 scopus 로고    scopus 로고
    • Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis-related protein Mac-2 BP/90K
    • Becker R, Lenter MC, Vollkommer T, Boos AM, Pfaff D, et al. (2008) Tumor stroma marker endosialin (Tem1) is a binding partner of metastasis-related protein Mac-2 BP/90K. FASEB Journal 22: 3059-3067.
    • (2008) FASEB Journal , vol.22 , pp. 3059-3067
    • Becker, R.1    Lenter, M.C.2    Vollkommer, T.3    Boos, A.M.4    Pfaff, D.5
  • 41
    • 78650182530 scopus 로고    scopus 로고
    • UVB-irradiation regulates VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 under flow conditions
    • Wang L, Shirure VS, Burdick MM, Wu S, (2011) UVB-irradiation regulates VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 under flow conditions. Molecular Carcinogenesis 50: 58-65.
    • (2011) Molecular Carcinogenesis , vol.50 , pp. 58-65
    • Wang, L.1    Shirure, V.S.2    Burdick, M.M.3    Wu, S.4
  • 43
    • 79958297186 scopus 로고    scopus 로고
    • Multiple immunofluorescence labeling of formalin-fixed paraffin-embedded tissue
    • Robertson D, Isacke CM, (2011) Multiple immunofluorescence labeling of formalin-fixed paraffin-embedded tissue. Methods in Molecular Biology 724: 69-77.
    • (2011) Methods in Molecular Biology , vol.724 , pp. 69-77
    • Robertson, D.1    Isacke, C.M.2
  • 44
    • 33845764296 scopus 로고    scopus 로고
    • A guided tour into subcellular colocalization analysis in light microscopy
    • Bolte S, Cordelieres FP, (2006) A guided tour into subcellular colocalization analysis in light microscopy. Journal of Microscopy-Oxford 224: 213-232.
    • (2006) Journal of Microscopy-Oxford , vol.224 , pp. 213-232
    • Bolte, S.1    Cordelieres, F.P.2
  • 45
    • 0027229657 scopus 로고
    • Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain
    • Koths K, Taylor E, Halenbeck R, Casipit C, Wang A, (1993) Cloning and characterization of a human Mac-2-binding protein, a new member of the superfamily defined by the macrophage scavenger receptor cysteine-rich domain. Journal of Biological Chemistry 268: 14245-14249.
    • (1993) Journal of Biological Chemistry , vol.268 , pp. 14245-14249
    • Koths, K.1    Taylor, E.2    Halenbeck, R.3    Casipit, C.4    Wang, A.5
  • 47
    • 0029914159 scopus 로고    scopus 로고
    • Sialyl Lewis (x)/E-selectin-mediated rolling in a cell-free system
    • Brunk D, Goetz D, Hammer D, (1996) Sialyl Lewis (x)/E-selectin-mediated rolling in a cell-free system. Biophysical Journal 71: 2902-2907.
    • (1996) Biophysical Journal , vol.71 , pp. 2902-2907
    • Brunk, D.1    Goetz, D.2    Hammer, D.3
  • 48
    • 0033863821 scopus 로고    scopus 로고
    • Role of metastatic potential in the adhesion of human breast cancer cells to endothelial monolayers
    • Moss MA, Zimmer S, Anderson KW, (2000) Role of metastatic potential in the adhesion of human breast cancer cells to endothelial monolayers. Anticancer Research 20: 1425-1433.
    • (2000) Anticancer Research , vol.20 , pp. 1425-1433
    • Moss, M.A.1    Zimmer, S.2    Anderson, K.W.3
  • 49
    • 13544263379 scopus 로고    scopus 로고
    • CD44 cross-linking induces integrin-mediated adhesion and transendothelial migration in breast cancer cell line by up-regulation of LFA-1 (alpha L beta2) and VLA-4 (alpha4beta1)
    • Wang HS, Hung Y, Su CH, Peng ST, Guo YJ, et al. (2005) CD44 cross-linking induces integrin-mediated adhesion and transendothelial migration in breast cancer cell line by up-regulation of LFA-1 (alpha L beta2) and VLA-4 (alpha4beta1). Experimental Cell Research 304: 116-126.
    • (2005) Experimental Cell Research , vol.304 , pp. 116-126
    • Wang, H.S.1    Hung, Y.2    Su, C.H.3    Peng, S.T.4    Guo, Y.J.5
  • 51
    • 0036569698 scopus 로고    scopus 로고
    • Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients
    • Marchetti A, Tinari N, Buttitta F, Chella A, Angeletti CA, et al. (2002) Expression of 90K (Mac-2 BP) correlates with distant metastasis and predicts survival in stage I non-small cell lung cancer patients. Cancer research 62: 2535-2539.
    • (2002) Cancer Research , vol.62 , pp. 2535-2539
    • Marchetti, A.1    Tinari, N.2    Buttitta, F.3    Chella, A.4    Angeletti, C.A.5
  • 53
    • 0030030905 scopus 로고    scopus 로고
    • Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins
    • Frenette PS, Mayadas TN, Rayburn H, Hynes RO, Wagner DD, (1996) Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins. Cell 84: 563-574.
    • (1996) Cell , vol.84 , pp. 563-574
    • Frenette, P.S.1    Mayadas, T.N.2    Rayburn, H.3    Hynes, R.O.4    Wagner, D.D.5
  • 55
    • 0030030009 scopus 로고    scopus 로고
    • Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on endothelial cells of hematopoietic tissues
    • Schweitzer KM, Drager AM, Van der Valk P, Thijsen SF, Zevenbergen A, et al. (1996) Constitutive expression of E-selectin and vascular cell adhesion molecule-1 on endothelial cells of hematopoietic tissues. American Journal of Pathology 148: 165-175.
    • (1996) American Journal of Pathology , vol.148 , pp. 165-175
    • Schweitzer, K.M.1    Drager, A.M.2    van der Valk, P.3    Thijsen, S.F.4    Zevenbergen, A.5
  • 56
    • 0028074969 scopus 로고
    • Regulation of Secretion and Surface Expression of Mac-2, a Galactoside-Binding Protein of Macrophages
    • Sato S, Hughes RC, (1994) Regulation of Secretion and Surface Expression of Mac-2, a Galactoside-Binding Protein of Macrophages. Journal of Biological Chemistry 269: 4424-4430.
    • (1994) Journal of Biological Chemistry , vol.269 , pp. 4424-4430
    • Sato, S.1    Hughes, R.C.2
  • 57
    • 45949102754 scopus 로고    scopus 로고
    • Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow
    • Cooper D, Norling LV, Perretti M, (2008) Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. Journal of Leukocyte Biology 83: 1459-1466.
    • (2008) Journal of Leukocyte Biology , vol.83 , pp. 1459-1466
    • Cooper, D.1    Norling, L.V.2    Perretti, M.3
  • 58
    • 12144285871 scopus 로고    scopus 로고
    • Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege
    • Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, et al. (2004) Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege. Cancer Cell 5: 241-251.
    • (2004) Cancer Cell , vol.5 , pp. 241-251
    • Rubinstein, N.1    Alvarez, M.2    Zwirner, N.W.3    Toscano, M.A.4    Ilarregui, J.M.5


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.