Targeting selectins and their ligands in cancer

Frontiers in Oncology

Volumn 6, Issue APR, 2016, Pages

  Natoni, Alessandro ^a   Macauley, Matthew S ^b   O'Dwyer, Michael E ^a  

^a NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Glycomimetic; Glycosylation; Metastasis; Niche; Selectin; Sialic acid; Sialyltransferase; Tumor

Indexed keywords

ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; FUCOSYLTRANSFERASE; GMI 1271; PADGEM PROTEIN; RIVIPANSEL; SELECTIN; SELECTIN ANTAGONIST; SIALYLTRANSFERASE; UNCLASSIFIED DRUG;

CELL HOMING; CELL INTERACTION; CELL SELF-RENEWAL; DRUG MECHANISM; DRUG TARGETING; GENE OVEREXPRESSION; HUMAN; METASTASIS; NEOPLASM; NONHUMAN; PROTEIN STRUCTURE; REVIEW; STEM CELL NICHE; TUMOR EMBOLISM; TUMOR MICROENVIRONMENT;

EID: 84973539287     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2016.00093     Document Type: Review

References (111)

1. Carvalho S, Catarino TA, Dias AM, Kato M, Almeida A, Hessling B, et al. Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer. Oncogene (2016) 35:1619-31. doi:10.1038/onc.2015.225
2. Stowell SR, Ju T, Cummings RD. Protein glycosylation in cancer. Annu Rev Pathol (2015) 10:473-510. doi:10.1146/annurev-pathol-012414-040438
3. Reymond N, d'Agua BB, Ridley AJ. Crossing the endothelial barrier during metastasis. Nat Rev Cancer (2013) 13:858-70. doi:10.1038/nrc3628
4. Dennis JW, Granovsky M, Warren CE. Glycoprotein glycosylation and cancer progression. Biochim Biophys Acta (1999) 1473:21-34. doi:10.1016/S0304-4165(99)00167-1
5. Freire-de-Lima L. Sweet and sour: the impact of differential glycosylation in cancer cells undergoing epithelial-mesenchymal transition. Front Oncol (2014) 4:59. doi:10.3389/fonc.2014.00059
6. Hauselmann I, Borsig L. Altered tumor-cell glycosylation promotes metastasis. Front Oncol (2014) 4:28. doi:10.3389/fonc.2014.00028
7. Glavey SV, Huynh D, Reagan MR, Manier S, Moschetta M, Kawano Y, et al. The cancer glycome: carbohydrates as mediators of metastasis. Blood Rev (2015) 29:269-79. doi:10.1016/j.blre.2015.01.003
8. Bull C, Stoel MA, den Brok MH, Adema GJ. Sialic acids sweeten a tumor's life. Cancer Res (2014) 74:3199-204. doi:10.1158/0008-5472.CAN-14-0728
9. Schultz MJ, Swindall AF, Bellis SL. Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev (2012) 31:501-18. doi:10.1007/s10555-012-9359-7
10. Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P. The human sialyltransferase family. Biochimie (2001) 83:727-37. doi:10.1016/S0300-9084(01)01301-3
11. Datta AK. Comparative sequence analysis in the sialyltransferase protein family: analysis of motifs. Curr Drug Targets (2009) 10:483-98. doi:10.2174/138945009788488422
12. Takashima S, Tsuji S. Functional diversity of mammalian sialyltransferases. Trends Glycosci Glycotechnol (2011) 23:178-93. doi:10.4052/tigg.23.178
13. Cohen M, Varki A. The sialome-far more than the sum of its parts. OMICS (2010) 14:455-64. doi:10.1089/omi.2009.0148
14. Harduin-Lepers A, Mollicone R, Delannoy P, Oriol R. The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach. Glycobiology (2005) 15:805-17. doi:10.1093/glycob/cwi063
15. Rao FV, Rich JR, Rakic B, Buddai S, Schwartz MF, Johnson K, et al. Structural insight into mammalian sialyltransferases. Nat Struct Mol Biol (2009) 16:1186-8. doi:10.1038/nsmb.1685
16. Kuhn B, Benz J, Greif M, Engel AM, Sobek H, Rudolph MG. The structure of human alpha-2,6-sialyltransferase reveals the binding mode of complex glycans. Acta Crystallogr D Biol Crystallogr (2013) 69:1826-38. doi:10.1107/S0907444913015412
17. Meng L, Forouhar F, Thieker D, Gao Z, Ramiah A, Moniz H, et al. Enzymatic basis for N-glycan sialylation: structure of rat alpha2,6-sialyltransferase (ST6GAL1) reveals conserved and unique features for glycan sialylation. J Biol Chem (2013) 288:34680-98. doi:10.1074/jbc.M113.519041
18. Volkers G, Worrall LJ, Kwan DH, Yu CC, Baumann L, Lameignere E, et al. Structure of human ST8SiaIII sialyltransferase provides insight into cell-surface polysialylation. Nat Struct Mol Biol (2015) 22:627-35. doi:10.1038/nsmb.3060
19. Harduin-Lepers A, Krzewinski-Recchi MA, Colomb F, Foulquier F, Groux-Degroote S, Delannoy P. Sialyltransferases functions in cancers. Front Biosci (Elite Ed) (2012) 4:499-515. doi:10.2741/E396
20. Bull C, den Brok MH, Adema GJ. Sweet escape: sialic acids in tumor immune evasion. Biochim Biophys Acta (2014) 1846:238-46. doi:10.1016/j.bbcan.2014.07.005
21. Dall'Olio F, Malagolini N, Trinchera M, Chiricolo M. Sialosignaling: sialyltransferases as engines of self-fueling loops in cancer progression. Biochim Biophys Acta (2014) 1840:2752-64. doi:10.1016/j.bbagen.2014.06.006
22. Bull C, Boltje TJ, van Dinther EAW, Peters T, de Graaf AMA, Leusen JHW, et al. Targeted delivery of a sialic acid-blocking glycomimetic to cancer cells inhibits metastatic spread. ACS Nano (2015) 9:733-45. doi:10.1021/nn5061964
23. Vajaria BN, Patel KR, Begum R, Patel PS. Sialylation: an avenue to target cancer cells. Pathol Oncol Res (2015) 1-5. doi:10.1007/s12253-015-0033-6
24. Pearce OM, Laubli H. Sialic acids in cancer biology and immunity. Glycobiology (2016) 26:111-28. doi:10.1093/glycob/cwv097
25. Chong YK, Sandanaraj E, Koh LW, Thangaveloo M, Tan MS, Koh GR, et al. ST3GAL1-associated transcriptomic program in glioblastoma tumor growth, invasion, and prognosis. J Natl Cancer Inst (2015) 108:djv326. doi:10.1093/jnci/djv326
26. Hedlund M, Ng E, Varki A, Varki NM. Alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo. Cancer Res (2008) 68:388-94. doi:10.1158/0008-5472.CAN-07-1340
27. Antony P, Rose M, Heidenreich A, Knuchel R, Gaisa NT, Dahl E. Epigenetic inactivation of ST6GAL1 in human bladder cancer. BMC Cancer (2014) 14:901. doi:10.1186/1471-2407-14-901
28. Lee M, Lee HJ, Bae S, Lee YS. Protein sialylation by sialyltransferase involves radiation resistance. Mol Cancer Res (2008) 6:1316-25. doi:10.1158/1541-7786.MCR-07-2209
29. Myers DD, Wrobleski SK, Kelsey K, Farris D, Jose DA, Peter HK, et al. E-selectin inhibitor GMI-1271 works in combination with low-molecular weight heparin to decrease venous thrombosis and bleeding risk in a mouse model. Blood (2014) 124:593
30. Hudak JE, Canham SM, Bertozzi CR. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat Chem Biol (2014) 10:69-75. doi:10.1038/nchembio.1388
31. Jandus C, Boligan KF, Chijioke O, Liu H, Dahlhaus M, Demoulins T, et al. Interactions between Siglec-7/9 receptors and ligands influence NK cell-dependent tumor immunosurveillance. J Clin Invest (2014) 124:1810-20. doi:10.1172/JCI65899
32. Laubli H, Pearce OM, Schwarz F, Siddiqui SS, Deng L, Stanczak MA, et al. Engagement of myelomonocytic Siglecs by tumor-associated ligands modulates the innate immune response to cancer. Proc Natl Acad Sci U S A (2014) 111:14211-6. doi:10.1073/pnas.1409580111
33. Hamamura K, Furukawa K, Hayashi T, Hattori T, Nakano J, Nakashima H, et al. Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells. Proc Natl Acad Sci U S A (2005) 102:11041-6. doi:10.1073/pnas.0503658102
34. Seales EC, Jurado GA, Brunson BA, Wakefield JK, Frost AR, Beilis SL. Hypersialylation of beta(1) integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility. Cancer Res (2005) 65:4645-52. doi:10.1158/0008-5472.CAN-04-3117
35. Azab AK, Quang P, Azab F, Pitsillides C, Thompson B, Chonghaile T, et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood (2012) 119:1468-78. doi:10.1182/blood-2011-07-368050
36. Glavey SV, Manier S, Natoni A, Sacco A, Moschetta M, Reagan MR, et al. The sialyltransferase ST3GAL6 influences homing and survival in multiple myeloma. Blood (2014) 124:1765-76. doi:10.1182/blood-2014-03-560862
37. Julien S, Ivetic A, Grigoriadis A, QiZe D, Burford B, Sproviero D, et al. Selectin ligand sialyl-Lewis X antigen drives metastasis of hormone-dependent breast cancers. Cancer Res (2011) 71:7683-93. doi:10.1158/0008-5472.CAN-11-1139
38. Tozawa K, Okamoto T, Kawai N, Hashimoto Y, Hayashi Y, Kohri K. Positive correlation between sialyl Lewis X expression and pathologic findings in renal cell carcinoma. Kidney Int (2005) 67:1391-6. doi:10.1111/j.1523-1755.2005.00216.x
39. Fukuoka K, Narita N, Saijo N. Increased expression of sialyl Lewis(x) antigen is associated with distant metastasis in lung cancer patients: immunohistochemical study on bronchofiberscopic biopsy specimens. Lung Cancer (1998) 20:109-16. doi:10.1016/S0169-5002(98)00016-6
40. Patel KD, Cuvelier SL, Wiehler S. Selectins: critical mediators of leukocyte recruitment. Semin Immunol (2002) 14:73-81. doi:10.1006/smim.2001.0344
41. Sperandio M. Selectins and glycosyltransferases in leukocyte rolling in vivo. FEBS J (2006) 273:4377-89. doi:10.1111/j.1742-4658.2006.05437.x
42. Gout S, Tremblay PL, Huot J. Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis. Clin Exp Metastasis (2008) 25:335-44. doi:10.1007/s10585-007-9096-4
43. Witz IP. The selectin-selectin ligand axis in tumor progression. Cancer Metastasis Rev (2008) 27:19-30. doi:10.1007/s10555-007-9101-z
44. Laubli H, Borsig L. Selectins promote tumor metastasis. Semin Cancer Biol (2010) 20:169-77. doi:10.1016/j.semcancer.2010.04.005
45. Bendas G, Borsig L. Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol (2012) 2012:676731. doi:10.1155/2012/676731
46. Heidemann F, Schildt A, Schmid K, Bruns OT, Riecken K, Jung C, et al. Selectins mediate small cell lung cancer systemic metastasis. PLoS One (2014) 9:e92327. doi:10.1371/journal.pone.0092327
47. Ben-David T, Sagi-Assif O, Meshel T, Lifshitz V, Yron I, Witz IP. The involvement of the sLe-a selectin ligand in the extravasation of human colorectal carcinoma cells. Immunol Lett (2008) 116:218-24. doi:10.1016/j.imlet.2007.11.022
48. Geng Y, Yeh K, Takatani T, King MR. Three to tango: MUC1 as a ligand for both E-selectin and ICAM-1 in the breast cancer metastatic cascade. Front Oncol (2012) 2:76. doi:10.3389/fonc.2012.00076
49. Li J, Guillebon AD, Hsu JW, Barthel SR, Dimitroff CJ, Lee YF, et al. Human fucosyltransferase 6 enables prostate cancer metastasis to bone. Br J Cancer (2013) 109:3014-22. doi:10.1038/bjc.2013.690
50. Muz B, Azab F, de la Puente P, Rollins S, Alvarez R, Kawar Z, et al. Inhibition of P-Selectin and PSGL-1 using humanized monoclonal antibodies increases the sensitivity of multiple myeloma cells to Bortezomib. Biomed Res Int (2015) 2015:417586. doi:10.1155/2015/417586
51. Natoni A, Smith TAG, Keane N, Locatelli-Hoops SC, Oliva I, Fogler WE, et al. E-selectin ligand expression increases with progression of myeloma and induces drug resistance in a murine transplant model, which is overcome by the glycomimetic E-selectin antagonist, GMI-1271. Blood (2015) 126:1805
52. Chien S, Haq SU, Pawlus M, Moon RT, Estey EH, Appelbaum FR, et al. Adhesion of acute myeloid leukemia blasts to E-selectin in the vascular niche enhances their survival by mechanisms such as wnt activation. Blood (2013) 122:61
53. Gakhar G, Navarro VN, Jurish M, Lee GY, Tagawa ST, Akhtar NH, et al. Circulating tumor cells from prostate cancer patients interact with E-selectin under physiologic blood flow. PLoS One (2013) 8:e85143. doi:10.1371/journal.pone.0085143
54. Biancone L, Araki M, Araki K, Vassalli P, Stamenkovic I. Redirection of tumor metastasis by expression of E-selectin in vivo. J Exp Med (1996) 183:581-7. doi:10.1084/jem.183.2.581
55. Brodt P, Fallavollita L, Bresalier RS, Meterissian S, Norton CR, Wolitzky BA. Liver endothelial E-selectin mediates carcinoma cell adhesion and promotes liver metastasis. Int J Cancer (1997) 71:612-9. doi:10.1002/(SICI)1097-0215(19970516)71:4<612::AID-IJC17>3.3.CO;2-1
56. Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, et al. Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci U S A (2011) 108:3725-30. doi:10.1073/pnas.1100446108
57. Khatib AM, Fallavollita L, Wancewicz EV, Monia BP, Brodt P. Inhibition of hepatic endothelial E-selectin expression by C-raf antisense oligonucleotides blocks colorectal carcinoma liver metastasis. Cancer Res (2002) 62:5393-8
58. Wicklein D, Schmidt A, Labitzky V, Ullrich S, Valent P, Schumacher U. E-and p-selectins are essential for repopulation of chronic myelogenous and chronic eosinophilic leukemias in a scid mouse xenograft model. PLoS One (2013) 8:e70139. doi:10.1371/journal.pone.0070139
59. Krause DS, Lazarides K, Lewis JB, von Andrian UH, Van Etten RA. Selectins and their ligands are required for homing and engraftment of BCR-ABL1+ leukemic stem cells in the bone marrow niche. Blood (2014) 123:1361-71. doi:10.1182/blood-2013-11-538694
60. Lafouresse F, Bellard E, Laurent C, Moussion C, Fournie JJ, Ysebaert L, et al. L-selectin controls trafficking of chronic lymphocytic leukemia cells in lymph node high endothelial venules in vivo. Blood (2015) 126:1336-45. doi:10.1182/blood-2015-02-626291
61. Laubli H, Stevenson JL, Varki A, Varki NM, Borsig L. L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res (2006) 66:1536-42. doi:10.1158/0008-5472.CAN-05-3121
62. Laubli H, Borsig L. Selectins as mediators of lung metastasis. Cancer Microenviron (2010) 3:97-105. doi:10.1007/s12307-010-0043-6
63. Zollner O, Lenter MC, Blanks JE, Borges E, Steegmaier M, Zerwes HG, et al. L-selectin from human, but not from mouse neutrophils binds directly to E-selectin. J Cell Biol (1997) 136:707-16. doi:10.1083/jcb.136.3.707
64. Jutila MA, Kurk S, Jackiw L, Knibbs RN, Stoolman LM. L-selectin serves as an E-selectin ligand on cultured human T lymphoblasts. J Immunol (2002) 169:1768-73. doi:10.4049/jimmunol.169.4.1768
65. Hoos A, Protsyuk D, Borsig L. Metastatic growth progression caused by PSGL-1-mediated recruitment of monocytes to metastatic sites. Cancer Res (2014) 74:695-704. doi:10.1158/0008-5472.CAN-13-0946
66. Coupland LA, Chong BH, Parish CR. Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells. Cancer Res (2012) 72:4662-71. doi:10.1158/0008-5472.CAN-11-4010
67. Kannagi R. Molecular mechanism for cancer-associated induction of sialyl Lewis X and sialyl Lewis A expression-the Warburg effect revisited. Glycoconj J (2004) 20:353-64. doi:10.1023/B:GLYC.0000033631.35357.41
68. Koike T, Kimura N, Miyazaki K, Yabuta T, Kumamoto K, Takenoshita S, et al. Hypoxia induces adhesion molecules on cancer cells: a missing link between Warburg effect and induction of selectin-ligand carbohydrates. Proc Natl Acad Sci U S A (2004) 101:8132-7. doi:10.1073/pnas.0402088101
69. Natoni A, Moschetta M, Glavey S, Wu P, Morgan GJ, Joshi L, et al. Multiple myeloma cells express functional E-selectin ligands which can be inhibited both in-vitro and in-vivo leading to prolongation of survival in a murine transplant model. Blood (2014) 124:4718
70. Hakomori S, Kannagi R. Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst (1983) 71:231-51
71. Hakomori S. Tumor-associated glycolipid antigens, their metabolism and organization. Chem Phys Lipids (1986) 42:209-33. doi:10.1016/0009-3084(86)90054-X
72. Sakuma K, Aoki M, Kannagi R. Transcription factors c-Myc and CDX2 mediate E-selectin ligand expression in colon cancer cells undergoing EGF/bFGF-induced epithelial-mesenchymal transition. Proc Natl Acad Sci U S A (2012) 109:7776-81. doi:10.1073/pnas.1111135109
73. Li N. Platelets in cancer metastasis: to help the "villain" to do evil. Int J Cancer (2016) 138:2078-87. doi:10.1002/ijc.29847
74. Hoffman R, Haim N, Brenner B. Cancer and thrombosis revisited. Blood Rev (2001) 15:61-7. doi:10.1054/blre.2001.0149
75. Cooke NM, Egan K, McFadden S, Grogan L, Breathnach OS, O'Leary J, et al. Increased platelet reactivity in patients with late-stage metastatic cancer. Cancer Med (2013) 2:564-70. doi:10.1002/cam4.86
76. Tesfamariam B. Involvement of platelets in tumor cell metastasis. Pharmacol Ther (2016) 157:112-9. doi:10.1016/j.pharmthera.2015.11.005
77. Kim YJ, Borsig L, Varki NM, Varki A. P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci U S A (1998) 95:9325-30. doi:10.1073/pnas.95.16.9325
78. Ludwig RJ, Boehme B, Podda M, Henschler R, Jager E, Tandi C, et al. Endothelial P-selectin as a target of heparin action in experimental melanoma lung metastasis. Cancer Res (2004) 64:2743-50. doi:10.1158/0008-5472.CAN-03-1054
79. Geng Y, Chandrasekaran S, Hsu JW, Gidwani M, Hughes AD, King MR. Phenotypic switch in blood: effects of pro-inflammatory cytokines on breast cancer cell aggregation and adhesion. PLoS One (2013) 8:e54959. doi:10.1371/journal.pone.0054959
80. Sceneay J, Smyth MJ, Moller A. The pre-metastatic niche: finding common ground. Cancer Metastasis Rev (2013) 32:449-64. doi:10.1007/s10555-013-9420-1
81. Smith HA, Kang Y. The metastasis-promoting roles of tumor-associated immune cells. J Mol Med (Berl) (2013) 91:411-29. doi:10.1007/s00109-013-1021-5
82. Laubli H, Spanaus KS, Borsig L. Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes. Blood (2009) 114:4583-91. doi:10.1182/blood-2008-10-186585
83. Winkler IG, Barbier V, Nowlan B, Jacobsen RN, Forristal CE, Patton JT, et al. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat Med (2012) 18:1651-7. doi:10.1038/nm.2969
84. Winkler IG, Barbier V, Pattabiraman DR, Gonda TJ, Magnani JL, Levesque JP. Vascular niche E-selectin protects acute myeloid leukaemia stem cells from chemotherapy. Blood (2014) 124:516
85. Aggoune D, Magnani JL, Van Etten RA, Krause DS. The vascular niche is involved in regulating leukemic stem cells in murine chronic myelogenous leukemia. Blood (2014) 124:516
86. Wang L, Liu Y, Wu L, Sun XL. Sialyltransferase inhibition and recent advances. Biochim Biophys Acta (2016) 1864:143-53. doi:10.1016/j.bbapap.2015.07.007
87. Gloster TM, Zandberg WF, Heinonen JE, Shen DL, Deng L, Vocadlo DJ. Hijacking a biosynthetic pathway yields a glycosyltransferase inhibitor within cells. Nat Chem Biol (2011) 7:174-81. doi:10.1038/nchembio.520
88. Rillahan CD, Antonopoulos A, Lefort CT, Sonon R, Azadi P, Ley K, et al. Global metabolic inhibitors of sialyl-and fucosyltransferases remodel the glycome. Nat Chem Biol (2012) 8:661-8. doi:10.1038/nchembio.999
89. Burkart MD, Vincent SP, Duffels A, Murray BW, Ley SV, Wong CH. Chemo-enzymatic synthesis of fluorinated sugar nucleotide: useful mechanistic probes for glycosyltransferases. Bioorg Med Chem (2000) 8:1937-46. doi:10.1016/S0968-0896(00)00139-5
90. Macauley MS, Arlian BM, Rillahan CD, Pang PC, Bortell N, Marcondes MC, et al. Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases. J Biol Chem (2014) 289:35149-58. doi:10.1074/jbc.M114.606517
91. Bull C, Boltje TJ, Wassink M, de Graaf AMA, van Delft FL, den Brok MH, et al. Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth. Mol Cancer Ther (2013) 12:1935-46. doi:10.1158/1535-7163.MCT-13-0279
92. Galeano B, Klootwijk R, Manoli I, Sun M, Ciccone C, Darvish D, et al. Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine. J Clin Invest (2007) 117:1585-94. doi:10.1172/JCI30954
93. Zheng Y, Yang J, Qian J, Qiu P, Hanabuchi S, Lu Y, et al. PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma. Leukemia (2013) 27:702-10. doi:10.1038/leu.2012.272
94. Yue Z, Wang A, Zhu Z, Tao L, Li Y, Zhou L, et al. Holothurian glycosaminoglycan inhibits metastasis via inhibition of P-selectin in B16F10 melanoma cells. Mol Cell Biochem (2015) 410:143-54. doi:10.1007/s11010-015-2546-4
95. Borsig L. Heparin as an inhibitor of cancer progression. Prog Mol Biol Transl Sci (2010) 93:335-49. doi:10.1016/S1877-1173(10)93014-7
96. Borsig L. Antimetastatic activities of heparins and modified heparins. Experimental evidence. Thromb Res (2010) 125(Suppl 2):S66-71. doi:10.1016/S0049-3848(10)70017-7
97. Gomes AM, Kozlowski EO, Borsig L, Teixeira FC, Vlodavsky I, Pavao MS. Antitumor properties of a new non-anticoagulant heparin analog from the mollusk Nodipecten nodosus: effect on P-selectin, heparanase, metastasis and cellular recruitment. Glycobiology (2015) 25:386-93. doi:10.1093/glycob/cwu119
98. Borsig L, Vlodavsky I, Ishai-Michaeli R, Torri G, Vismara E. Sulfated hexasaccharides attenuate metastasis by inhibition of P-selectin and heparanase. Neoplasia (2011) 13:445-52. doi:10.1593/neo.101734
99. Kozlowski EO, Pavao MS, Borsig L. Ascidian dermatan sulfates attenuate metastasis, inflammation and thrombosis by inhibition of P-selectin. J Thromb Haemost (2011) 9:1807-15. doi:10.1111/j.1538-7836.2011.04401.x
100. Esposito M, Magnani JL, Kang YB. Exploration of a potent E-selectin antagonist (GMI-1271) as a potential novel therapeutic for treating breast cancer metastasis to the bone and lung. Cancer Res (2014) 74:4039. doi:10.1158/1538-7445.AM2014-4039
101. Steele MM, Radhakrishnan P, Magnani JL, Hollingsworth MA. A small molecule glycomimetic antagonist of E-selectin (GMI-1271) prevents pancreatic tumor metastasis and offers a novel treatment for improved efficacy of chemotherapy. Cancer Res (2014) 74:4503. doi:10.1158/1538-7445.AM2014-4503
102. Price T, Burness M, Sivan A, Cheng R, Magnani JL, Sipkins DA. Breast cancer cells metastasize to bone through E-selectin+ vascular gateways. Cancer Res (2014) 74:4831. doi:10.1158/1538-7445.AM2014-4831
103. Devata S, Sood SL, Hemmer MV, Flanner H, Kramer W, Nietubicz C, et al. First in human phase 1 single dose escalation studies of the E-selectin antagonist GMI-1271 show a favorable safety, pharmacokinetic, and biomarker profile. Blood (2015) 126:1004
104. Winkler IG, Barbier V, Nutt HL, Hasnain SZ, Levesque JP, Magnani JL, et al. Administration of E-selectin antagonist GMI-1271 improves survival after high-dose chemotherapy by alleviating mucositis and accelerating neutrophil recovery. Blood (2013) 122:2266
105. Gravina GL, Mancini A, Colapietro A, Monache SD, Angelucci A, Calgani A, et al. Dual E-selectin and CXCR4 inhibition reduces tumor growth and increases the sensitivity to docetaxel in experimental bone metastases of prostate cancer. Cancer Res (2015) 75:428. doi:10.1158/1538-7445.AM2015-428
106. Steele MM, Fogler WF, Magnani JL, Hollingsworth MA. A small molecule glycomimetic antagonist of E-selectin and CXCR4 (GMI-1359) prevents pancreatic tumor metastasis and improves chemotherapy. Cancer Res (2015) 75:425. doi:10.1158/1538-7445.AM2015-425
107. Zhang W, Patel N, Fogler WE, Magnani JL, Andreeff M. The dual E-selectin/CXCR4 inhibitor, GMI-1359, enhances efficacy of anti-leukemia chemotherapy in FLT3-ITD mutated acute myeloid leukemia. Blood (2015) 126:3790
108. Shamay Y, Raviv L, Golan M, Voronov E, Apte RN, David A. Inhibition of primary and metastatic tumors in mice by E-selectin-targeted polymer-drug conjugates. J Control Release (2015) 217:102-12. doi:10.1016/j.jconrel.2015.08.029
109. Chen Y, Peng J, Han M, Omar M, Hu D, Ke X, et al. A low-molecular-weight heparin-coated doxorubicin-liposome for the prevention of melanoma metastasis. J Drug Target (2015) 23:335-46. doi:10.3109/1061186X.2014.996760
110. Mitchell MJ, Wayne E, Rana K, Schaffer CB, King MR. TRAIL-coated leukocytes that kill cancer cells in the circulation. Proc Natl Acad Sci U S A (2014) 111:930-5. doi:10.1073/pnas.1316312111
111. Wayne EC, Chandrasekaran S, Mitchell MJ, Chan MF, Lee RE, Schaffer CB, et al. TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer. J Control Release (2016) 223:215-23. doi:10.1016/j.jconrel.2015.12.048