The FASEB Journal, Vol 7, 1434-1441, Copyright © 1993 by The Federation of American Societies for Experimental Biology

REVIEWS

Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis

WG Stetler-Stevenson, LA Liotta and DE Kleiner Jr
Laboratory of Pathology, National Cancer Institute, DCBDC, National Institutes of Health, Bethesda, Maryland 20892.

Tumor invasion and metastasis formation are major obstacles for successful cancer therapy. Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extracellular matrix. A model system for tumor invasion of extracellular matrix barriers has been developed, and application of this model has facilitated our understanding of the molecular mechanisms of metastasis formation. This model consists of three steps: tumor cell adhesion, extracellular matrix proteolysis, and cell migration. The role of the matrix metalloprotease enzymes in tumor cell- mediated extracellular matrix proteolysis is well established. We review the functional domain structure of the matrix metalloprotease enzymes in general and specifically the interaction of metastasis- associated gelatinase A (72-kDa type IV collagenase) with the tissue inhibitor of metalloproteases-2 (TIMP-2). We also discuss the physiologic activation of the matrix metalloprotease enzymes and the specific cellular mechanism of action of gelatinase A.

This article has been cited by other articles:

				M. J. Kean, K. C. Williams, M. Skalski, D. Myers, A. Burtnik, D. Foster, and M. G. Coppolino VAMP3, syntaxin-13 and SNAP23 are involved in secretion of matrix metalloproteinases, degradation of the extracellular matrix and cell invasion J. Cell Sci., November 15, 2009; 122(22): 4089 - 4098. [Abstract] [Full Text] [PDF]

				J. G. Weinger, K. M. Omari, K. Marsden, C. S. Raine, and B. Shafit-Zagardo Up-Regulation of Soluble Axl and Mer Receptor Tyrosine Kinases Negatively Correlates with Gas6 in Established Multiple Sclerosis Lesions Am. J. Pathol., July 1, 2009; 175(1): 283 - 293. [Abstract] [Full Text] [PDF]

				E. Peiretti, S. Dessi, C. Mulas, C. Abete, C. Norfo, M. Putzolu, and M. Fossarello Modulation of Cholesterol Homeostasis by Antiproliferative Drugs in Human Pterygium Fibroblasts Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3450 - 3458. [Abstract] [Full Text] [PDF]

				A. Gurlek, N. Karavitaki, O. Ansorge, and J. A H Wass What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics Eur. J. Endocrinol., February 1, 2007; 156(2): 143 - 153. [Abstract] [Full Text] [PDF]

				C. F. Chantrain, H. Shimada, S. Jodele, S. Groshen, W. Ye, D. R. Shalinsky, Z. Werb, L. M. Coussens, and Y. A. DeClerck Stromal Matrix Metalloproteinase-9 Regulates the Vascular Architecture in Neuroblastoma by Promoting Pericyte Recruitment Cancer Res., March 1, 2004; 64(5): 1675 - 1686. [Abstract] [Full Text] [PDF]

				U. B. Hofmann, A. A. O. Eggert, K. Blass, E.-B. Brocker, and J. C. Becker Expression of Matrix Metalloproteinases in the Microenvironment of Spontaneous and Experimental Melanoma Metastases Reflects the Requirements for Tumor Formation Cancer Res., December 1, 2003; 63(23): 8221 - 8225. [Abstract] [Full Text] [PDF]

				H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]

				Y. Takahashi, T. Teshima, N. Kawaguchi, Y. Hamada, S. Mori, A. Madachi, S. Ikeda, H. Mizuno, T. Ogata, K. Nojima, et al. Heavy Ion Irradiation Inhibits in Vitro Angiogenesis Even at Sublethal Dose Cancer Res., July 15, 2003; 63(14): 4253 - 4257. [Abstract] [Full Text] [PDF]

				T. Masui, R. Doi, T. Koshiba, K. Fujimoto, S. Tsuji, S. Nakajima, M. Koizumi, E. Toyoda, S. Tulachan, D. Ito, et al. RECK Expression in Pancreatic Cancer: Its Correlation with Lower Invasiveness and Better Prognosis Clin. Cancer Res., May 1, 2003; 9(5): 1779 - 1784. [Abstract] [Full Text] [PDF]

				M. Colombi, N. Zoppi, G. De Petro, E. Marchina, R. Gardella, D. Tavian, S. Ferraboli, and S. Barlati Matrix Assembly Induction and Cell Migration and Invasion Inhibition by a 13-Amino Acid Fibronectin Peptide J. Biol. Chem., April 11, 2003; 278(16): 14346 - 14355. [Abstract] [Full Text] [PDF]

				S. Philip and G. C. Kundu Osteopontin Induces Nuclear Factor kappa B-mediated Promatrix Metalloproteinase-2 Activation through Ikappa Balpha /IKK Signaling Pathways, and Curcumin (Diferulolylmethane) Down-regulates These Pathways J. Biol. Chem., April 11, 2003; 278(16): 14487 - 14497. [Abstract] [Full Text] [PDF]

				D. L. Allen, D. H. Teitelbaum, and K. Kurachi Growth factor stimulation of matrix metalloproteinase expression and myoblast migration and invasion in vitro Am J Physiol Cell Physiol, April 1, 2003; 284(4): C805 - C815. [Abstract] [Full Text] [PDF]

				Z Liu and J Klominek Regulation of matrix metalloprotease activity in malignant mesothelioma cell lines by growth factors Thorax, March 1, 2003; 58(3): 198 - 203. [Abstract] [Full Text] [PDF]

				A. Valenzuela-Fernandez, T. Planchenault, F. Baleux, I. Staropoli, K. Le-Barillec, D. Leduc, T. Delaunay, F. Lazarini, J.-L. Virelizier, M. Chignard, et al. Leukocyte Elastase Negatively Regulates Stromal Cell-derived Factor-1 (SDF-1)/CXCR4 Binding and Functions by Amino-terminal Processing of SDF-1 and CXCR4 J. Biol. Chem., May 3, 2002; 277(18): 15677 - 15689. [Abstract] [Full Text] [PDF]

				G. A. Wood and M. C. Archer Matrix Metalloproteinases-2 and 9 Do Not Play a Role in the Growth of Preneoplastic Liver Lesions in F344 Rats Experimental Biology and Medicine, September 1, 2001; 226(8): 799 - 803. [Abstract] [Full Text] [PDF]

				J. Laitakari and F. Stenback Collagen Matrix in Development and Progression of Experimentally Induced Respiratory Neoplasms in the Hamster Toxicol Pathol, August 1, 2001; 29(5): 514 - 527. [Abstract] [PDF]

				M. N. Holten-Andersen, R. W. Stephens, H. J. Nielsen, G. Murphy, I. J. Christensen, W. Stetler-Stevenson, and N. Brunner High Preoperative Plasma Tissue Inhibitor of Metalloproteinase-1 Levels Are Associated with Short Survival of Patients with Colorectal Cancer Clin. Cancer Res., November 1, 2000; 6(11): 4292 - 4299. [Abstract] [Full Text] [PDF]

				P. E. Van den Steen, P. Proost, A. Wuyts, J. Van Damme, and G. Opdenakker Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact Blood, October 15, 2000; 96(8): 2673 - 2681. [Abstract] [Full Text] [PDF]

				K. Brand, A. H. Baker, A. Perez-Cantó, A. Possling, M. Sacharjat, M. Geheeb, and W. Arnold Treatment of Colorectal Liver Metastases by Adenoviral Transfer of Tissue Inhibitor of Metalloproteinases-2 into the Liver Tissue Cancer Res., October 1, 2000; 60(20): 5723 - 5730. [Abstract] [Full Text]

				H. Q. Ye, M. Maeda, F.-S. X. Yu, and D. T. Azar Differential Expression of MT1-MMP (MMP-14) and Collagenase III (MMP-13) Genes in Normal and Wounded Rat Corneas Invest. Ophthalmol. Vis. Sci., September 1, 2000; 41(10): 2894 - 2899. [Abstract] [Full Text]

				H. E. Turner, Zs. Nagy, M. M. Esiri, A. L. Harris, and J. A. H. Wass Role of Matrix Metalloproteinase 9 in Pituitary Tumor Behavior J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2931 - 2935. [Abstract] [Full Text]

				A. Béliveau, M. Bérubé, A. Rousseau, G. Pelletier, and S. L. Guérin Expression of Integrin {alpha}5{beta}1 and MMPs Associated with Epithelioid Morphology and Malignancy of Uveal Melanoma Invest. Ophthalmol. Vis. Sci., July 1, 2000; 41(8): 2363 - 2372. [Abstract] [Full Text]

				K. Asosingh, U. Gunthert, M. H. C. Bakkus, H. De Raeve, E. Goes, I. Van Riet, B. Van Camp, and K. Vanderkerken In Vivo Induction of Insulin-like Growth Factor-I Receptor and CD44v6 Confers Homing and Adhesion to Murine Multiple Myeloma Cells Cancer Res., June 1, 2000; 60(11): 3096 - 3104. [Abstract] [Full Text] [PDF]

				N. Varo, M. J. Iraburu, M. Varela, B. Lopez, J. C. Etayo, and J. Diez Chronic AT1 Blockade Stimulates Extracellular Collagen Type I Degradation and Reverses Myocardial Fibrosis in Spontaneously Hypertensive Rats Hypertension, June 1, 2000; 35(6): 1197 - 1202. [Abstract] [Full Text] [PDF]

				W. R. English, X. S. Puente, J. M. P. Freije, V. Knauper, A. Amour, A. Merryweather, C. Lopez-Otin, and G. Murphy Membrane Type 4 Matrix Metalloproteinase (MMP17) Has Tumor Necrosis Factor-alpha Convertase Activity but Does Not Activate Pro-MMP2 J. Biol. Chem., May 5, 2000; 275(19): 14046 - 14055. [Abstract] [Full Text] [PDF]

				Y. Sun, J. M. Cheung, J. Martel-Pelletier, J. P. Pelletier, L. Wenger, R. D. Altman, D. S. Howell, and H. S. Cheung Wild Type and Mutant p53 Differentially Regulate the Gene Expression of Human Collagenase-3 (hMMP-13) J. Biol. Chem., April 6, 2000; 275(15): 11327 - 11332. [Abstract] [Full Text] [PDF]

				S. Kanda, M. Kuzuya, M. A. Ramos, T. Koike, K. Yoshino, S. Ikeda, and A. Iguchi Matrix Metalloproteinase and {alpha}v{beta}3 Integrin-Dependent Vascular Smooth Muscle Cell Invasion Through a Type I Collagen Lattice Arterioscler Thromb Vasc Biol, April 1, 2000; 20(4): 998 - 1005. [Abstract] [Full Text] [PDF]

				S. Miyata, N. Koshikawa, H. Yasumitsu, and K. Miyazaki Trypsin Stimulates Integrin alpha 5beta 1-dependent Adhesion to Fibronectin and Proliferation of Human Gastric Carcinoma Cells through Activation of Proteinase-activated Receptor-2 J. Biol. Chem., February 18, 2000; 275(7): 4592 - 4598. [Abstract] [Full Text] [PDF]

				E. K. Rowinsky, R. Humphrey, L. A. Hammond, C. Aylesworth, L. Smetzer, M. Hidalgo, M. Morrow, L. Smith, A. Garner, J. M. Sorensen, et al. Phase I and Pharmacologic Study of the Specific Matrix Metalloproteinase Inhibitor BAY 12-9566 on a Protracted Oral Daily Dosing Schedule in Patients With Solid Malignancies J. Clin. Oncol., January 5, 2000; 18(1): 178 - 178. [Abstract] [Full Text] [PDF]

				M. P. Pereda, M. F. Ledda, V. Goldberg, A. Chervín, G. Carrizo, H. Molina, A. Müller, U. Renner, O. Podhajcer, E. Arzt, et al. High Levels of Matrix Metalloproteinases Regulate Proliferation and Hormone Secretion in Pituitary Cells J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 263 - 269. [Abstract] [Full Text]

				S. Pasco, J. Han, P. Gillery, G. Bellon, F.-X. Maquart, J. P. Borel, N. A. Kefalides, and J. C. Monboisse A Specific Sequence of the Noncollagenous Domain of the {{alpha}}3(IV) Chain of Type IV Collagen Inhibits Expression and Activation of Matrix Metalloproteinases by Tumor Cells Cancer Res., January 1, 2000; 60(2): 467 - 473. [Abstract] [Full Text]

				J. E. Park, M. C. Lenter, R. N. Zimmermann, P. Garin-Chesa, L. J. Old, and W. J. Rettig Fibroblast Activation Protein, a Dual Specificity Serine Protease Expressed in Reactive Human Tumor Stromal Fibroblasts J. Biol. Chem., December 17, 1999; 274(51): 36505 - 36512. [Abstract] [Full Text] [PDF]

				S. M. Arnold, A. B. Young, R. K. Munn, R. A. Patchell, N. Nanayakkara, and W. R. Markesbery Expression of p53, bcl-2, E-Cadherin, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 in Paired Primary Tumors and Brain Metastasis Clin. Cancer Res., December 1, 1999; 5(12): 4028 - 4033. [Abstract] [Full Text] [PDF]

				L. Zhang, S. Kharbanda, S. W. McLeskey, and F. G. Kern Overexpression of Fibroblast Growth Factor 1 in MCF-7 Breast Cancer Cells Facilitates Tumor Cell Dissemination but Does Not Support the Development of Macrometastases in the Lungs or Lymph Nodes Cancer Res., October 1, 1999; 59(19): 5023 - 5029. [Abstract] [Full Text] [PDF]

				U. Benbow, M. P. Schoenermark, T. I. Mitchell, J. L. Rutter, K.-i. Shimokawa, H. Nagase, and C. E. Brinckerhoff A Novel Host/Tumor Cell Interaction Activates Matrix Metalloproteinase 1 and Mediates Invasion through Type I Collagen J. Biol. Chem., September 3, 1999; 274(36): 25371 - 25378. [Abstract] [Full Text] [PDF]

				S. Koochekpour, M. Jeffers, P. H. Wang, C. Gong, G. A. Taylor, L. M. Roessler, R. Stearman, J. R. Vasselli, W. G. Stetler-Stevenson, W. G. Kaelin Jr., et al. The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells Mol. Cell. Biol., September 1, 1999; 19(9): 5902 - 5912. [Abstract] [Full Text] [PDF]

				Y. Kanamori, M. Matsushima, T. Minaguchi, K. Kobayashi, S. Sagae, R. Kudo, N. Terakawa, and Y. Nakamura Correlation between Expression of the Matrix Metalloproteinase-1 Gene in Ovarian Cancers and an Insertion/Deletion Polymorphism in Its Promoter Region Cancer Res., September 1, 1999; 59(17): 4225 - 4227. [Abstract] [Full Text] [PDF]

				F. Martin, S. Neil, J. Kupsch, M. Maurice, F.-L. Cosset, and M. Collins Retrovirus Targeting by Tropism Restriction to Melanoma Cells J. Virol., August 1, 1999; 73(8): 6923 - 6929. [Abstract] [Full Text]

				M. L. Coker, M. A. Doscher, C. V. Thomas, Z. S. Galis, and F. G. Spinale Matrix metalloproteinase synthesis and expression in isolated LV myocyte preparations Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H777 - H787. [Abstract] [Full Text] [PDF]

				K.L. Pickett, G.J. Harber, A.A. DeCarlo, P. Louis, S. Shaneyfelt, L.J. Windsor, and M.K. Bodden 92K-GL (MMP-9) and 72K-GL (MMP-2) are Produced in vivo by Human Oral Squamous Cell Carcinomas and can Enhance FIB-CL (MMP-1) Activity in vitro Journal of Dental Research, July 1, 1999; 78(7): 1354 - 1361. [Abstract] [PDF]

				R. Montesano, J. V. Soriano, G. Hosseini, M. S. Pepper, and H. Schramek Constitutively Active Mitogen-activated Protein Kinase Kinase MEK1 Disrupts Morphogenesis and Induces an Invasive Phenotype in Madin-Darby Canine Kidney Epithelial Cells Cell Growth Differ., May 1, 1999; 10(5): 317 - 332. [Abstract] [Full Text]

				C. Ries, F. Loher, C. Zang, M. G. Ismair, and P. E. Petrides Matrix Metalloproteinase Production by Bone Marrow Mononuclear Cells from Normal Individuals and Patients with Acute and Chronic Myeloid Leukemia or Myelodysplastic Syndromes Clin. Cancer Res., May 1, 1999; 5(5): 1115 - 1124. [Abstract] [Full Text] [PDF]

				M. Morita, N. Yoshiuchi, H. Arakawa, and S. Nishimura CMAP: A Novel Cystatin-like Gene Involved in Liver Metastasis Cancer Res., January 1, 1999; 59(1): 151 - 158. [Abstract] [Full Text] [PDF]

				U. Benbow, R. Maitra, J. W. Hamilton, and C. E. Brinckerhoff Selective Modulation of Collagenase 1 Gene Expression by the Chemotherapeutic Agent Doxorubicin Clin. Cancer Res., January 1, 1999; 5(1): 203 - 208. [Abstract] [Full Text] [PDF]

				G I Murray, M E Duncan, E Arbuckle, W T Melvin, and J E Fothergill Matrix metalloproteinases and their inhibitors in gastric cancer Gut, December 1, 1998; 43(6): 791 - 797. [Abstract] [Full Text] [PDF]

				E.A. Seftor, R.E.B. Seftor, D.R.C. Nieva, and M.J.C. Hendrix Application of Chemically Modified Tetracyclines (CMTs) in Experimental Models of Cancer and Arthritis Advances in Dental Research, November 1, 1998; 12(1): 103 - 110. [PDF]

				T. Kinoshita, H. Sato, A. Okada, E. Ohuchi, K. Imai, Y. Okada, and M. Seiki TIMP-2 Promotes Activation of Progelatinase A by Membrane-type 1 Matrix Metalloproteinase Immobilized on Agarose Beads J. Biol. Chem., June 26, 1998; 273(26): 16098 - 16103. [Abstract] [Full Text] [PDF]

				T. Hurskainen, M. Seiki, S. S. Apte, M. Syrjakallio-Ylitalo, T. Sorsa, A. Oikarinen, and H. Autio-Harmainen Production of Membrane-type Matrix Metalloproteinase-1 (MT-MMP-1) in Early Human Placenta: A Possible Role in Placental Implantation? J. Histochem. Cytochem., February 1, 1998; 46(2): 221 - 230. [Abstract] [Full Text]

				R. Jemtland, K. Lee, and G. V. Segre Heterogeneity Among Cells That Express Osteoclast-Associated Genes in Developing Bone Endocrinology, January 1, 1998; 139(1): 340 - 349. [Abstract] [Full Text] [PDF]

				S. S. Apte, N. Fukai, D. R. Beier, and B. R. Olsen The Matrix Metalloproteinase-14 (MMP-14) Gene Is Structurally Distinct from Other MMP Genes and Is Co-expressed with the TIMP-2 Gene during Mouse Embryogenesis J. Biol. Chem., October 10, 1997; 272(41): 25511 - 25517. [Abstract] [Full Text] [PDF]

				E. Duhamel-Clerin, C. Orvain, F. Lanza, J.-P. Cazenave, and C. Klein-Soyer Thrombin Receptor-Mediated Increase of Two Matrix Metalloproteinases, MMP-1 and MMP-3, in Human Endothelial Cells Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 1931 - 1938. [Abstract] [Full Text]

				M.C. DeRuiter, R.E. Poelmann, J.C. VanMunsteren, V. Mironov, R.R. Markwald, and A.C. Gittenberger-de Groot Embryonic Endothelial Cells Transdifferentiate Into Mesenchymal Cells Expressing Smooth Muscle Actins In Vivo and In Vitro Circ. Res., April 19, 1997; 80(4): 444 - 451. [Abstract] [Full Text]

				D. Hasenstab, R. Forough, and A. W. Clowes Plasminogen Activator Inhibitor Type 1 and Tissue Inhibitor of Metalloproteinases-2 Increase After Arterial Injury in Rats Circ. Res., April 19, 1997; 80(4): 490 - 496. [Abstract] [Full Text]

				Z. S. Galis, R. Kranzhofer, J. W. Fenton II, and P. Libby Thrombin Promotes Activation of Matrix Metalloproteinase-2 Produced by Cultured Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 1997; 17(3): 483 - 489. [Abstract] [Full Text]

				R.D. Kenagy, S. Vergel, E. Mattsson, M. Bendeck, M.A. Reidy, and A.W. Clowes The Role of Plasminogen, Plasminogen Activators, and Matrix Metalloproteinases in Primate Arterial Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, November 1, 1996; 16(11): 1373 - 1382. [Abstract] [Full Text]

				Lás. Bányai, H. Tordai, and Lás. Patthy Structure and Domain-Domain Interactions of the Gelatin-binding Site of Human 72-Kilodalton Type IV Collagenase (Gelatinase A, Matrix Metalloproteinase 2) J. Biol. Chem., May 17, 1996; 271(20): 12003 - 12008. [Abstract] [Full Text] [PDF]

				J. Couet, S. Sar, A. Jolivet, M.-T. V. Hai, E. Milgrom, and M. Misrahi Shedding of Human Thyrotropin Receptor Ectodomain J. Biol. Chem., February 23, 1996; 271(8): 4545 - 4552. [Abstract] [Full Text] [PDF]

				H Kinoh, H Sato, Y Tsunezuka, T Takino, A Kawashima, Y Okada, and M Seiki MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis J. Cell Sci., January 5, 1996; 109(5): 953 - 959. [Abstract] [PDF]

				N. Zempo, N. Koyama, R. D. Kenagy, H. J. Lea, and A. W. Clowes Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor Arterioscler Thromb Vasc Biol, January 1, 1996; 16(1): 28 - 33. [Abstract] [Full Text]

				C. M. Dollery, J. R. McEwan, and A. M. Henney Matrix Metalloproteinases and Cardiovascular Disease Circ. Res., November 1, 1995; 77(5): 863 - 868. [Full Text]

				N Boujrad, S. Ogwuegbu, M Garnier, C. Lee, B. Martin, and V Papadopoulos Identification of a stimulator of steroid hormone synthesis isolated from testis Science, June 16, 1995; 268(5217): 1609 - 1612. [Abstract] [PDF]

				A. Y. Strongin, I. Collier, G. Bannikov, B. L. Marmer, G. A. Grant, and G. I. Goldberg Mechanism Of Cell Surface Activation Of 72-kDa Type IV Collagenase J. Biol. Chem., March 10, 1995; 270(10): 5331 - 5338. [Abstract] [Full Text] [PDF]

				Y. Zhuge and J. Xu Rac1 Mediates Type I Collagen-dependent MMP-2 Activation. ROLE IN CELL INVASION ACROSS COLLAGEN BARRIER J. Biol. Chem., May 4, 2001; 276(19): 16248 - 16256. [Abstract] [Full Text] [PDF]

				S. Philip, A. Bulbule, and G. C. Kundu Osteopontin Stimulates Tumor Growth and Activation of Promatrix Metalloproteinase-2 through Nuclear Factor-kappa B-mediated Induction of Membrane Type 1 Matrix Metalloproteinase in Murine Melanoma Cells J. Biol. Chem., November 21, 2001; 276(48): 44926 - 44935. [Abstract] [Full Text] [PDF]