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Pacific Northwest Research Foundation, Biomembrane Division, Seattle, Washington 98122, and Departments of Pathobiology and Microbiology, University of Washington, Seattle, Washington 98195
Aberrant glycosylation expressed in glycosphingolipids and glycoproteins in tumor cells has been implicated as an essential mechanism in defining stage, direction, and fate of tumor progression. This general concept is supported by results from three lines of study:
Various reagents that block carbohydrate-mediated tumor cell adhesion or block glycosylation processing have been shown to inhibit tumor cell metastasis. This provides the basis for further development of "anti-adhesion therapy." Ganglioside analogues and sphingolipid analogues that inhibit protein kinase C and receptor-associated tyrosine kinase have been applied for inhibition of metastasis. A crucial mechanism for inhibition of metastasis by these reagents may involve blocking of transmembrane signaling for expression of P- and E-selectin. This provides the basis for development of "ortho-signaling therapy."
1 The author's own studies cited in this paper were supported by National Cancer Institute Outstanding Investigator Grant CA42505.
2 To whom requests for reprints should be addressed, at Pacific Northwest Research Foundation, Biomembrane Division, 720 Broadway, Seattle, WA 98122. Phone: (206) 726-1222; Fax: (206) 726-1212.
Received 9/ 9/96. Accepted 9/27/96.
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J. Mengwasser and J. P. Sleeman Expression of M-N#1, a histo-blood group B-like antigen, is strongly up-regulated in nonapoptosing mammary epithelial cells during rat mammary gland involution Glycobiology, June 1, 2001; 11(6): 441 - 449. [Abstract] [Full Text] [PDF] |
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K. Kumamoto, Y. Goto, K. Sekikawa, S. Takenoshita, N. Ishida, M. Kawakita, and R. Kannagi Increased Expression of UDP-Galactose Transporter Messenger RNA in Human Colon Cancer Tissues and Its Implication in Synthesis of Thomsen-Friedenreich Antigen and Sialyl Lewis A/X Determinants Cancer Res., June 1, 2001; 61(11): 4620 - 4627. [Abstract] [Full Text] [PDF] |
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L. Borsig, R. Wong, J. Feramisco, D. R. Nadeau, N. M. Varki, and A. Varki Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis PNAS, March 13, 2001; 98(6): 3352 - 3357. [Abstract] [Full Text] [PDF] |
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J. Li, D. M. Rancour, M. L. Allende, C. A. Worth, D. S. Darling, J. B. Gilbert, A. K. Menon, and W. W. Young Jr. The DXD motif is required for GM2 synthase activity but is not critical for nucleotide binding Glycobiology, March 1, 2001; 11(3): 217 - 229. [Abstract] [Full Text] [PDF] |
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E. Machida, J. Nakayama, J. Amano, and M. Fukuda Clinicopathological Significance of Core 2 {beta}1,6-N-Acetylglucosaminyltransferase Messenger RNA Expressed in the Pulmonary Adenocarcinoma Determined by in Situ Hybridization Cancer Res., March 1, 2001; 61(5): 2226 - 2231. [Abstract] [Full Text] |
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G. Zeng, L. Gao, S. Birklé, and R. K. Yu Suppression of Ganglioside GD3 Expression in a Rat F-11 Tumor Cell Line Reduces Tumor Growth, Angiogenesis, and Vascular Endothelial Growth Factor Production Cancer Res., December 1, 2000; 60(23): 6670 - 6676. [Abstract] [Full Text] |
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C. Zuber, M. J. Spiro, B. Guhl, R. G. Spiro, and J. Roth Golgi Apparatus Immunolocalization of Endomannosidase Suggests Post-Endoplasmic Reticulum Glucose Trimming: Implications for Quality Control Mol. Biol. Cell, December 1, 2000; 11(12): 4227 - 4240. [Abstract] [Full Text] |
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M. Meichenin, J. Rocher, O. Galanina, N. Bovin, N. Nifantev, A. Sherman, E. Cassagnau, M. F. Heymann, J. Bara, R. H. Fraser, et al. Tk, a New Colon Tumor-associated Antigen Resulting from Altered O-Glycosylation Cancer Res., October 1, 2000; 60(19): 5499 - 5507. [Abstract] [Full Text] |
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K.-A. Karlsson The human gastric colonizer Helicobacter pylori: a challenge for host-parasite glycobiology Glycobiology, August 1, 2000; 10(8): 761 - 771. [Abstract] [Full Text] [PDF] |
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W. Deng, R. Li, and S. Ladisch Influence of Cellular Ganglioside Depletion on Tumor Formation J Natl Cancer Inst, June 7, 2000; 92(11): 912 - 917. [Abstract] [Full Text] [PDF] |
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C. Goupille, S. Marionneau, V. Bureau, F. Hallouin, M. Meichenin, J. Rocher, and J. Le Pendu {alpha}1,2Fucosyltransferase increases resistance to apoptosis of rat colon carcinoma cells Glycobiology, April 1, 2000; 10(4): 375 - 382. [Abstract] [Full Text] [PDF] |
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M. Izawa, K. Kumamoto, C. Mitsuoka, A. Kanamori, K. Ohmori, H. Ishida, S. Nakamura, K. Kurata-Miura, K. Sasaki, T. Nishi, et al. Expression of Sialyl 6-Sulfo Lewis X Is Inversely Correlated with Conventional Sialyl Lewis X Expression in Human Colorectal Cancer Cancer Res., March 1, 2000; 60(5): 1410 - 1416. [Abstract] [Full Text] |
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M. Aubert, L. Panicot, C. Crotte, P. Gibier, D. Lombardo, M.-O. Sadoulet, and E. Mas Restoration of {{alpha}}(1,2) Fucosyltransferase Activity Decreases Adhesive and Metastatic Properties of Human Pancreatic Cancer Cells Cancer Res., March 1, 2000; 60(5): 1449 - 1456. [Abstract] [Full Text] |
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H. Yamamoto, J. Swoger, S. Greene, T. Saito, J. Hurh, C. Sweeley, J. Leestma, E. Mkrdichian, L. Cerullo, A. Nishikawa, et al. {beta}1,6-N-Acetylglucosamine-bearing N-Glycans in Human Gliomas: Implications for a Role in Regulating Invasivity Cancer Res., January 1, 2000; 60(1): 134 - 142. [Abstract] [Full Text] |
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T. Ichikawa, J. Nakayama, N. Sakura, T. Hashimoto, M. Fukuda, M. N. Fukuda, and T. Taki Expression of N-acetyllactosamine and {beta}1,4-Galactosyltransferase ({beta}4GalT-I) During Adenoma-Carcinoma Sequence in the Human Colorectum J. Histochem. Cytochem., December 1, 1999; 47(12): 1593 - 1602. [Abstract] [Full Text] |
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E. Rapoport and J. Pendu Glycosylation alterations ofcells in late phase apoptosis from colon carcinomas Glycobiology, December 1, 1999; 9(12): 1337 - 1345. [Abstract] [Full Text] [PDF] |
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M. G. Manfredi, S. Lim, K. P. Claffey, and T. N. Seyfried Gangliosides Influence Angiogenesis in an Experimental Mouse Brain Tumor Cancer Res., October 1, 1999; 59(20): 5392 - 5397. [Abstract] [Full Text] [PDF] |
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M. Mylvaganam and C. A. Lingwood A Convenient Oxidation of Natural Glycosphingolipids to Their "Ceramide Acids" for Neoglycoconjugation. BOVINE SERUM ALBUMIN-GLYCOSYLCERAMIDE ACID CONJUGATES AS INVESTIGATIVE PROBES FOR HIV gp120 COAT PROTEIN-GLYCOSPHINGOLIPID INTERACTIONS J. Biol. Chem., July 16, 1999; 274(29): 20725 - 20732. [Abstract] [Full Text] [PDF] |
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M. Rachkovsky and J. Pawelek Acquired Melanocyte Stimulating Hormone-inducible Chemotaxis following Macrophage Fusion with Cloudman S91 Melanoma Cells Cell Growth Differ., July 1, 1999; 10(7): 517 - 524. [Abstract] [Full Text] |
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S. Mao, C. Gao, C.-H. L. Lo, P. Wirsching, C.-H. Wong, and K. D. Janda Phage-display library selection of high-affinity human single-chain antibodies to tumor-associated carbohydrate antigens sialyl Lewisx and Lewisx PNAS, June 8, 1999; 96(12): 6953 - 6958. [Abstract] [Full Text] [PDF] |
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M. Ono, K. Handa, D. A. Withers, and S.-i. Hakomori Motility Inhibition and Apoptosis Are Induced by Metastasis-suppressing Gene Product CD82 and Its Analogue CD9, with Concurrent Glycosylation Cancer Res., May 1, 1999; 59(10): 2335 - 2339. [Abstract] [Full Text] [PDF] |
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R. Chammas, J. L. Sonnenburg, N. E. Watson, T. Tai, M. G. Farquhar, N. M. Varki, and A. Varki De-N-acetyl-gangliosides in Humans: Unusual Subcellular Distribution of a Novel Tumor Antigen Cancer Res., March 1, 1999; 59(6): 1337 - 1346. [Abstract] [Full Text] [PDF] |
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T. Sugiyama and Y. Sadzuka Combination of Theanine with Doxorubicin Inhibits Hepatic Metastasis of M5076 Ovarian Sarcoma Clin. Cancer Res., February 1, 1999; 5(2): 413 - 416. [Abstract] [Full Text] [PDF] |
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M. Peyrard, E. Seroussi, A.-C. Sandberg-Nordqvist, Y.-G. Xie, F.-Y. Han, I. Fransson, J. Collins, I. Dunham, M. Kost-Alimova, S. Imreh, et al. The human LARGE gene from 22q12.3-q13.1 is a new, distinct member of the glycosyltransferase gene family PNAS, January 19, 1999; 96(2): 598 - 603. [Abstract] [Full Text] [PDF] |
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E. J. Meuillet, R. Kroes, H. Yamamoto, T. G. Warner, J. Ferrari, B. Mania-Farnell, D. George, A. Rebbaa, J. R. Moskal, and E. G. Bremer Sialidase Gene Transfection Enhances Epidermal Growth Factor Receptor Activity in an Epidermoid Carcinoma Cell Line, A431 Cancer Res., January 1, 1999; 59(1): 234 - 240. [Abstract] [Full Text] [PDF] |
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Y. J. Kim, L. Borsig, N. M. Varki, and A. Varki P-selectin deficiency attenuates tumor growth and metastasis PNAS, August 4, 1998; 95(16): 9325 - 9330. [Abstract] [Full Text] [PDF] |
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M. M. Grilley, S. D. Stock, R. C. Dickson, R. L. Lester, and J. Y. Takemoto Syringomycin Action Gene SYR2 Is Essential for Sphingolipid 4-Hydroxylation in Saccharomyces cerevisiae J. Biol. Chem., May 1, 1998; 273(18): 11062 - 11068. [Abstract] [Full Text] [PDF] |
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B.-L. Wang, G. F. Springer, and S. C. Carlstedt Quantitative Computerized Image Analysis of Tn and T (Thomsen-Friedenreich) Epitopes in Prognostication of Human Breast Carcinoma J. Histochem. Cytochem., October 1, 1997; 45(10): 1393 - 1400. [Abstract] [Full Text] [PDF] |
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