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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2011, Vol. 5 Issue (4) : 336-340     DOI: 10.1007/s11684-011-0163-5
MINI-REVIEW |
Endostatin specifically targets both tumor blood vessels and lymphatic vessels
Wei Zhuo1,2,3, Yang Chen1,2,3, Xiaomin Song1,2,3, Yongzhang Luo1,2,3()
1. National Engineering Laboratory for Anti-tumor Protein Therapeutics, Beijing 100084, China; 2. Beijing Key Laboratory for Protein Therapeutics, Beijing 100084, China; 3. Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Abstract  

Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, was first identified as a potent angiogenic inhibitor. The anti-angiogenic function of endostatin has been well documented during the past decade. Recently, several studies demonstrated that endostatin also inhibits tumor lymphangiogenesis and lymphatic metastasis. However, the exact mechanism that endostatin executes its anti-angiogenic and anti-lymphangiogenic functions remains elusive. In the current mini-review, we briefly summarize recent novel findings, including the functions of endostatin targeting not only angiogenesis but also lymphangiogenesis, and the underlying mechanism by which endostatin internalization regulates its biological functions.

Keywords endostatin      angiogenesis      lymphangiogenesis      nystatin      internalization      tumor     
Corresponding Authors: Luo Yongzhang,Email:yluo@tsinghua.edu.cn   
Issue Date: 05 December 2011
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-011-0163-5     OR     http://academic.hep.com.cn/fmd/EN/Y2011/V5/I4/336
Fig.1  Two endocytic pathways are involved in endostatin internalization. One is the low-efficient caveola/lipid raft pathway, and the other is the high-efficient clathrin pathway. Nystatin treatment facilitates the translocation of endostatin out of caveola/lipid raft and switches endostatin internalization predominantly to the high-efficient clathrin-dependent pathway, resulting in enhanced endostatin overall uptake.
1 O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88(2): 277–285
doi: 10.1016/S0092-8674(00)81848-6 pmid:9008168
2 Folkman J. Antiangiogenesis in cancer therapy—endostatin and its mechanisms of action. Exp Cell Res 2006; 312(5): 594–607
doi: 10.1016/j.yexcr.2005.11.015 pmid:16376330
3 Fu Y, Chen Y, Luo X, Liang Y, Shi H, Gao L, Zhan S, Zhou D, Luo Y. The heparin binding motif of endostatin mediates its interaction with receptor nucleolin. Biochemistry 2009; 48(49): 11655–11663
doi: 10.1021/bi901265z pmid:19877579
4 Fu Y, Luo Y. The N-terminal integrity is critical for the stability and biological functions of endostatin. Biochemistry 2010; 49(30): 6420–6429
doi: 10.1021/bi100489x pmid:20545324
5 Fu Y, Tang H, Huang Y, Song N, Luo Y. Unraveling the mysteries of endostatin. IUBMB Life 2009; 61(6): 613–626
doi: 10.1002/iub.215 pmid:19472178
6 Fukumoto S, Morifuji M, Katakura Y, Ohishi M, Nakamura S. Endostatin inhibits lymph node metastasis by a down-regulation of the vascular endothelial growth factor C expression in tumor cells. Clin Exp Metastasis 2005; 22(1): 31–38
doi: 10.1007/s10585-005-3973-5 pmid:16132576
7 Brideau G, M?kinen MJ, Elamaa H, Tu H, Nilsson G, Alitalo K, Pihlajaniemi T, Heljasvaara R. Endostatin overexpression inhibits lymphangiogenesis and lymph node metastasis in mice. Cancer Res 2007; 67(24): 11528–11535
doi: 10.1158/0008-5472.CAN-07-1458 pmid:18089781
8 Zhuo W, Luo C, Wang X, Song X, Fu Y, Luo Y. Endostatin inhibits tumour lymphangiogenesis and lymphatic metastasis via cell surface nucleolin on lymphangiogenic endothelial cells. J Pathol 2010; 222(3): 249–260
doi: 10.1002/path.2760 pmid:20814900
9 Ou J, Li J, Pan F, Xie G, Zhou Q, Huang H, Liang H. Endostatin suppresses colorectal tumor-induced lymphangiogenesis by inhibiting expression of fibronectin extra domain A and integrin α9. J Cell Biochem 2011; 112(8): 2106–2114
doi: 10.1002/jcb.23130 pmid:21465533
10 Achen MG, McColl BK, Stacker SA. Focus on lymphangiogenesis in tumor metastasis. Cancer Cell 2005; 7(2): 121–127
doi: 10.1016/j.ccr.2005.01.017 pmid:15710325
11 Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature 2005; 438(7070): 946–953
doi: 10.1038/nature04480 pmid:16355212
12 Karpanen T, Alitalo K. Molecular biology and pathology of lymphangiogenesis. Annu Rev Pathol 2008; 3(1): 367–397
doi: 10.1146/annurev.pathmechdis.3.121806.151515 pmid:18039141
13 Cao R, Bj?rndahl MA, Religa P, Clasper S, Garvin S, Galter D, Meister B, Ikomi F, Tritsaris K, Dissing S, Ohhashi T, Jackson DG, Cao Y. PDGF-BB induces intratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell 2004; 6(4): 333–345
doi: 10.1016/j.ccr.2004.08.034 pmid:15488757
14 Kajiya K, Hirakawa S, Ma B, Drinnenberg I, Detmar M. Hepatocyte growth factor promotes lymphatic vessel formation and function. EMBO J 2005; 24(16): 2885–2895
doi: 10.1038/sj.emboj.7600763 pmid:16052207
15 Bj?rndahl M, Cao R, Nissen LJ, Clasper S, Johnson LA, Xue Y, Zhou Z, Jackson D, Hansen AJ, Cao Y. Insulin-like growth factors 1 and 2 induce lymphangiogenesis in vivo. Proc Natl Acad Sci USA 2005; 102(43): 15593–15598
doi: 10.1073/pnas.0507865102 pmid:16230630
16 Chang LK, Garcia-Carde?a G, Farnebo F, Fannon M, Chen EJ, Butterfield C, Moses MA, Mulligan RC, Folkman J, Kaipainen A. Dose-dependent response of FGF-2 for lymphangiogenesis. Proc Natl Acad Sci USA 2004; 101(32): 11658–11663
doi: 10.1073/pnas.0404272101 pmid:15289610
17 Shi H, Huang Y, Zhou H, Song X, Yuan S, Fu Y, Luo Y. Nucleolin is a receptor that mediates antiangiogenic and antitumor activity of endostatin. Blood 2007; 110(8): 2899–2906
doi: 10.1182/blood-2007-01-064428 pmid:17615292
18 Dixelius J, Larsson H, Sasaki T, Holmqvist K, Lu L, Engstr?m A, Timpl R, Welsh M, Claesson-Welsh L. Endostatin-induced tyrosine kinase signaling through the Shb adaptor protein regulates endothelial cell apoptosis. Blood 2000; 95(11): 3403–3411
pmid:10828022
19 MacDonald NJ, Shivers WY, Narum DL, Plum SM, Wingard JN, Fuhrmann SR, Liang H, Holland-Linn J, Chen DH, Sim BK. Endostatin binds tropomyosin: a potential modulator of the antitumor activity of endostatin. J Biol Chem 2001; 276(27): 25190–25196
doi: 10.1074/jbc.M100743200 pmid:11335715
20 Zhou H, Wang W, Luo Y. Contributions of disulfide bonds in a nested pattern to the structure, stability, and biological functions of endostatin. J Biol Chem 2005; 280(12): 11303–11312
doi: 10.1074/jbc.M412072200 pmid:15634676
21 Le Roy C, Wrana JL. Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling. Nat Rev Mol Cell Biol 2005; 6(2): 112–126
doi: 10.1038/nrm1571 pmid:15687999
22 Parton RG, Simons K. The multiple faces of caveolae. Nat Rev Mol Cell Biol 2007; 8(3): 185–194
doi: 10.1038/nrm2122 pmid:17318224
23 Pellinen T, Tuomi S, Arjonen A, Wolf M, Edgren H, Meyer H, Grosse R, Kitzing T, Rantala JK, Kallioniemi O, F?ssler R, Kallio M, Ivaska J. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell 2008; 15(3): 371–385
doi: 10.1016/j.devcel.2008.08.001 pmid:18804435
24 Shi F, Sottile J. Caveolin-1-dependent beta1 integrin endocytosis is a critical regulator of fibronectin turnover. J Cell Sci 2008; 121(14): 2360–2371
doi: 10.1242/jcs.014977 pmid:18577581
25 Caswell PT, Vadrevu S, Norman JC. Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 2009; 10(12): 843–853
doi: 10.1038/nrm2799 pmid:19904298
26 Chen Y, Wang S, Lu X, Zhang H, Fu Y, Luo Y. Cholesterol sequestration by nystatin enhances the uptake and activity of endostatin in endothelium via regulating distinct endocytic pathways. Blood 2011; 117(23): 6392–6403
doi: 10.1182/blood-2010-12-322867 pmid:21482707
27 Abdollahi A, Hahnfeldt P, Maercker C, Gr?ne HJ, Debus J, Ansorge W, Folkman J, Hlatky L, Huber PE. Endostatin’s antiangiogenic signaling network. Mol Cell 2004; 13(5): 649–663
doi: 10.1016/S1097-2765(04)00102-9 pmid:15023336
28 Bazigou E, Xie S, Chen C, Weston A, Miura N, Sorokin L, Adams R, Muro AF, Sheppard D, Makinen T. Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis. Dev Cell 2009; 17(2): 175–186
doi: 10.1016/j.devcel.2009.06.017 pmid:19686679
29 Christian S, Pilch J, Akerman ME, Porkka K, Laakkonen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell Biol 2003; 163(4): 871–878
doi: 10.1083/jcb.200304132 pmid:14638862
30 Huang Y, Shi H, Zhou H, Song X, Yuan S, Luo Y. The angiogenic function of nucleolin is mediated by vascular endothelial growth factor and nonmuscle myosin. Blood 2006; 107(9): 3564–3571
doi: 10.1182/blood-2005-07-2961 pmid:16403913
31 Boehm T, Folkman J, Browder T, O’Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997; 390(6658): 404–407
doi: 10.1038/37126 pmid:9389480
32 Herbst RS, Hess KR, Tran HT, Tseng JE, Mullani NA, Charnsangavej C, Madden T, Davis DW, McConkey DJ, O’Reilly MS, Ellis LM, Pluda J, Hong WK, Abbruzzese JL. Phase I study of recombinant human endostatin in patients with advanced solid tumors. J Clin Oncol 2002; 20(18): 3792–3803
doi: 10.1200/JCO.2002.11.061 pmid:12228199
33 Dong X, Zhao X, Xiao T, Tian H, Yun C. Endostar, a recombined humanized endostatin, inhibits lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenograft in mice. Thorac Cardiovasc Surg 2011; 59(3): 133–136
doi: 10.1055/s-0030-1250152 pmid:21480131
34 Jia Y, Liu M, Huang W, Wang Z, He Y, Wu J, Ren S, Ju Y, Geng R, Li Z.Recombinant human endostatin endostar inhibits tumor growth and metastasis in a mouse xenograft model of colon cancer. Pathol Oncol Res 2011Sep 22. [Epub ahead of print]
pmid:21938482
35 Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, Chappell J, Wilting J, Weich HA, Yamagami S, Amano S, Mizuki N, Alexander JS, Peterson ML, Brekken RA, Hirashima M, Capoor S, Usui T, Ambati BK, Ambati J. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med 2009; 15(9): 1023–1030
doi: 10.1038/nm.2018 pmid:19668192
36 Rehn M, Veikkola T, Kukk-Valdre E, Nakamura H, Ilmonen M, Lombardo C, Pihlajaniemi T, Alitalo K, Vuori K. Interaction of endostatin with integrins implicated in angiogenesis. Proc Natl Acad Sci USA 2001; 98(3): 1024–1029
doi: 10.1073/pnas.031564998 pmid:11158588
37 Karumanchi SA, Jha V, Ramchandran R, Karihaloo A, Tsiokas L, Chan B, Dhanabal M, Hanai JI, Venkataraman G, Shriver Z, Keiser N, Kalluri R, Zeng H, Mukhopadhyay D, Chen RL, Lander AD, Hagihara K, Yamaguchi Y, Sasisekharan R, Cantley L, Sukhatme VP. Cell surface glypicans are low-affinity endostatin receptors. Mol Cell 2001; 7(4): 811–822
doi: 10.1016/S1097-2765(01)00225-8 pmid:11336704
38 Sasaki T, Fukai N, Mann K, G?hring W, Olsen BR, Timpl R. Structure, function and tissue forms of the C-terminal globular domain of collagen XVIII containing the angiogenesis inhibitor endostatin. EMBO J 1998; 17(15): 4249–4256
doi: 10.1093/emboj/17.15.4249 pmid:9687493
39 Kim YM, Jang JW, Lee OH, Yeon J, Choi EY, Kim KW, Lee ST, Kwon YG. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase. Cancer Res 2000; 60(19): 5410–5413
pmid:11034081
40 Sudhakar A, Sugimoto H, Yang C, Lively J, Zeisberg M, Kalluri R. Human tumstatin and human endostatin exhibit distinct antiangiogenic activities mediated by alpha v beta 3 and alpha 5 beta 1 integrins. Proc Natl Acad Sci USA 2003; 100(8): 4766–4771
doi: 10.1073/pnas.0730882100 pmid:12682293
41 Wickstr?m SA, Alitalo K, Keski-Oja J. Endostatin associates with integrin alpha5beta1 and caveolin-1, and activates Src via a tyrosyl phosphatase-dependent pathway in human endothelial cells. Cancer Res 2002; 62(19): 5580–5589
pmid:12359771
42 Wickstr?m SA, Alitalo K, Keski-Oja J. Endostatin associates with lipid rafts and induces reorganization of the actin cytoskeleton via down-regulation of RhoA activity. J Biol Chem 2003; 278(39): 37895–37901
doi: 10.1074/jbc.M303569200 pmid:12851410
43 Anderson RG. The caveolae membrane system. Annu Rev Biochem 1998; 67(1): 199–225
doi: 10.1146/annurev.biochem.67.1.199 pmid:9759488
44 Zhang AY, Yi F, Zhang G, Gulbins E, Li PL. Lipid raft clustering and redox signaling platform formation in coronary arterial endothelial cells. Hypertension 2006; 47(1): 74–80
doi: 10.1161/10.1161/01.HYP.0000196727.53300.62 pmid:16344372
45 Jin S, Zhang Y, Yi F, Li PL. Critical role of lipid raft redox signaling platforms in endostatin-induced coronary endothelial dysfunction. Arterioscler Thromb Vasc Biol 2008; 28(3): 485–490
doi: 10.1161/ATVBAHA.107.159772 pmid:18162606
46 Said EA, Krust B, Nisole S, Svab J, Briand JP, Hovanessian AG. The anti-HIV cytokine midkine binds the cell surface-expressed nucleolin as a low affinity receptor. J Biol Chem 2002; 277(40): 37492–37502
doi: 10.1074/jbc.M201194200 pmid:12147681
47 Legrand D, Vigié K, Said EA, Elass E, Masson M, Slomianny MC, Carpentier M, Briand JP, Mazurier J, Hovanessian AG. Surface nucleolin participates in both the binding and endocytosis of lactoferrin in target cells. Eur J Biochem 2004; 271(2): 303–317
doi: 10.1046/j.1432-1033.2003.03929.x pmid:14717698
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