title: Inhibition of metastasis of syngeneic murine melanoma in vivo and vasculogenesis in vitro by monoclonal antibody C11C1 targeted to domain 5 of high molecular weight kininogen.
abstract: Metastasis of malignant tumors is a major cause of morbidity and mortality. Inhibition of tumor growth in distant organs is of clinical importance. We have demonstrated that C11C1, a murine monoclonal antibody to the light chain region of high molecular weight kininogen (HK), reduces growth of murine multiple myeloma in normal mice and human colon cancer in nude mice. C11C1 inhibits angiogenesis by reducing tumor microvascular density by blocking binding of HK to endothelial cells. We now evaluate the anti-metastatic effect of C11C1 on C57BL/6 mouse lung metastatic model using B16F10 melanoma cells. The tail veins of mice were injected with 0.5 × 10(6) cells of melanoma B16F10. One group received C11C1 and the other received saline (control) intraperitoneally. When mice were killed at 28 days, 6 of 10 control mice had detectable metastatic pulmonary nodules which stained positive with an antibody against S-100 protein, a tumor antigen present in malignant melanoma cells. In the C11C1 groups, none of the mice showed metastatic foci in their lungs. We showed that C11C1 inhibits endothelial cell tube formation in a 3-D collagen fibrinogen gel model by inhibiting the rate of cleavage of HK by plasma kallikrein without changing the binding affinity for HK. These studies demonstrate that a monoclonal antibody to HK has the potential to prevent metastasis with minimal side effects.
authors.affiliation: The Sol Sherry Thrombosis Research Center, Temple University School of Medicine, 3400 N. Broad Street, OMS 418, Philadelphia, PA 19140, USA.
authors.forename: Sabina T
authors.initials: ST
authors.lastname: Khan
authors.forename: Robin A
authors.initials: RA
authors.lastname: Pixley
authors.forename: Yuchuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Nadia
authors.initials: N
authors.lastname: Bakdash
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gordon
authors.forename: Alexis
authors.initials: A
authors.lastname: Agelan
authors.forename: Yajue
authors.initials: Y
authors.lastname: Huang
authors.forename: Mohan P
authors.initials: MP
authors.lastname: Achary
authors.forename: Robert W
authors.initials: RW
authors.lastname: Colman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D019679:Kininogen, High-Molecular-Weight / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D017434:Protein Structure, Tertiary
chemical_list: D000911:Antibodies, Monoclonal; D019679:Kininogen, High-Molecular-Weight
references.citation: Cell. 1997 Jan 24;88(2):277-85
references.pmid: 9008168
references.citation: Protein Sci. 1992 Jan;1(1):151-60
references.pmid: 1304876
references.citation: Cell Mol Life Sci. 2003 Mar;60(3):463-73
references.pmid: 12737307
references.citation: Arthritis Rheum. 1998 Jun;41(6):951-62
references.pmid: 9627005
references.citation: Biochem Biophys Res Commun. 1996 Sep 24;226(3):703-10
references.pmid: 8831678
references.citation: Blood. 2008 Feb 1;111(3):1274-81
references.pmid: 18000168
references.citation: Thromb Haemost. 1992 Aug 3;68(2):99-101
references.pmid: 1412176
references.citation: J Biol Chem. 2004 Apr 16;279(16):16621-8
references.pmid: 14764580
references.citation: Eur Respir J. 2000 Sep;16(3):452-8
references.pmid: 11028659
references.citation: Am J Pathol. 1999 Sep;155(3):887-95
references.pmid: 10487846
references.citation: J Biol Chem. 1997 Sep 26;272(39):24203-9
references.pmid: 9305872
references.citation: J Biol Chem. 1985 Jul 15;260(14):8610-7
references.pmid: 2989294
references.citation: Adv Cancer Res. 1991;57:273-328
references.pmid: 1950706
references.citation: FASEB J. 2001 Jun;15(8):1487-9
references.pmid: 11387266
references.citation: Cancer Immunol Immunother. 2006 Jul;55(7):797-807
references.pmid: 16187087
references.citation: Lab Invest. 2002 Jul;82(7):871-80
references.pmid: 12118089
references.citation: J Biol Chem. 1987 Jan 25;262(3):1405-11
references.pmid: 2433279
references.citation: J Clin Invest. 1984 Apr;73(4):954-62
references.pmid: 6561202
references.citation: J Clin Invest. 1997 Sep 15;100(6):1481-7
references.pmid: 9294114
references.citation: Diabetes Metab. 1996 Jul;22(4):268-73
references.pmid: 8767174
references.citation: J Thromb Haemost. 2003 Jan;1(1):164-70
references.pmid: 12871554
references.citation: J Biol Chem. 2001 May 11;276(19):16587-91
references.pmid: 11340086
references.citation: J Cell Sci. 1999 Dec;112 ( Pt 23):4213-21
references.pmid: 10564640
references.citation: J Cell Biol. 1991 Nov;115(4):1107-12
references.pmid: 1659573
references.citation: J Biol Chem. 2000 Jan 21;275(3):1521-4
references.pmid: 10636838
references.citation: J Clin Invest. 1997 Dec 15;100(12):3131-9
references.pmid: 9399960
references.citation: Blood. 2004 Oct 1;104(7):2065-72
references.pmid: 15161672
references.citation: J Biol Chem. 1993 Feb 5;268(4):2486-92
references.pmid: 8428925
references.citation: Trends Immunol. 2004 Aug;25(8):450-5
references.pmid: 15275645
references.citation: Microvasc Res. 1996 May;51(3):347-64
references.pmid: 8992233
references.citation: J Clin Invest. 1996 Jun 15;97(12):2792-802
references.pmid: 8675690
references.citation: Biochem Biophys Res Commun. 1989 Jan 16;158(1):72-9
references.pmid: 2783551
references.citation: Cell. 1994 Oct 21;79(2):315-28
references.pmid: 7525077
references.citation: Curr Opin Cell Biol. 1997 Oct;9(5):714-24
references.pmid: 9330876
references.citation: J Exp Med. 1994 May 1;179(5):1409-15
references.pmid: 7513008
references.citation: Circulation. 1999 Apr 6;99(13):1726-32
references.pmid: 10190883
references.citation: Int Immunopharmacol. 2002 Mar;2(4):499-509
references.pmid: 11962729
references.citation: Blood. 2000 Jan 15;95(2):543-50
references.pmid: 10627460
references.citation: Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1821-9
references.pmid: 11247797
references.citation: Thromb Haemost. 2007 Jul;98(1):77-83
references.pmid: 17597995