title: Antibody directed against human YKL-40 increases tumor volume in a human melanoma xenograft model in scid mice.
abstract: Induced overexpression of the secretory protein YKL-40 promotes tumor growth in xenograft experiments. We investigated if targeting YKL-40 with a monoclonal antibody could inhibit tumor growth. YKL-40 expressing human melanoma cells (LOX) were injected subcutenously in Balb/c scid mice. Animals were treated with intraperitoneal injections of anti-YKL-40, isoptype control or PBS. Non-YKL-40 expressing human pancreatic carcinoma cell line PaCa 5061 served as additional control. MR imaging was used for evaluation of tumor growth. Two days after the first injections of anti-YKL-40, tumor volume had increased significantly compared with controls, whereas no effects were observed for control tumors from PaCa 5061 cells lacking YKL-40 expression. After 18 days, mean tumor size of the mice receiving repeated anti-YKL-40 injections was 1.82 g, >4 times higher than mean tumor size of the controls (0.42 g). The effect of anti-YKL-40 on the increase of tumor volume started within hours after injection and was dose dependent. Intratumoral hemorrhage was observed in the treated animals. The strong effect on tumor size indicates important roles for YKL-40 in melanoma growth and argues for a careful evaluation of antibody therapy directed against YKL-40.
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Radiology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Salamon
authors.affiliation: Department of Interdisciplinary Endoscopy, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Hoffmann
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Elies
authors.affiliation: Department of Radiology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kersten
authors.initials: K
authors.lastname: Peldschus
authors.affiliation: Oncology and Medicine, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Lüers
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Schumacher
authors.affiliation: Institute of Anatomy and Experimental Morphology, University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
mesh_terms: D054392:Adipokines / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D000071451:Chitinase-3-Like Protein 1; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000276:immunology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D023041:Xenograft Model Antitumor Assays
chemical_list: D054392:Adipokines; D000911:Antibodies, Monoclonal; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins
references.citation: J Histochem Cytochem. 2007 Dec;55(12):1213-28
references.pmid: 17712177
references.citation: Genomics. 1997 Jul 15;43(2):221-5
references.pmid: 9244440
references.citation: Exp Cell Res. 2003 Jul 1;287(1):79-87
references.pmid: 12799184
references.citation: Lung Cancer. 2005 May;48(2):223-31
references.pmid: 15829322
references.citation: J Biol Chem. 2003 Sep 26;278(39):37753-60
references.pmid: 12851408
references.citation: Future Oncol. 2009 Sep;5(7):1065-82
references.pmid: 19792974
references.citation: Clin Chem. 2008 Mar;54(3):582-9
references.pmid: 18171715
references.citation: Biochem Biophys Res Commun. 2001 Jul 27;285(4):926-31
references.pmid: 11467840
references.citation: Br J Cancer. 2007 Feb 26;96(4):609-16
references.pmid: 17262079
references.citation: J Biol Chem. 2011 Apr 29;286(17):15332-43
references.pmid: 21385870
references.citation: Exp Cell Res. 1999 Jul 10;250(1):168-73
references.pmid: 10388530
references.citation: J Exp Med. 2009 May 11;206(5):1149-66
references.pmid: 19414556
references.citation: J Immunol. 2008 Oct 1;181(7):5167-73
references.pmid: 18802121
references.citation: J Biol Chem. 2006 Jul 28;281(30):21082-21095
references.pmid: 16704970
references.citation: Cancer. 2006 Mar 1;106(5):1130-9
references.pmid: 16456816
references.citation: J Clin Oncol. 2006 Feb 10;24(5):798-804
references.pmid: 16391295
references.citation: Mol Cancer Ther. 2011 May;10(5):742-51
references.pmid: 21357475
references.citation: Oncogene. 2009 Dec 17;28(50):4456-68
references.pmid: 19767768
references.citation: Mod Pathol. 2005 Jun;18(6):779-87
references.pmid: 15791284
references.citation: Clin Chem. 1998 Mar;44(3):509-16
references.pmid: 9510855
references.citation: J Biol Chem. 1993 Dec 5;268(34):25803-10
references.pmid: 8245017
references.citation: Int J Cancer. 1988 Mar 15;41(3):442-9
references.pmid: 3346110
references.citation: Br J Cancer. 2010 May 25;102(11):1555-77
references.pmid: 20502460
references.citation: Biochem J. 2002 Jul 1;365(Pt 1):119-26
references.pmid: 12071845
references.citation: Gastroenterology. 2006 Feb;130(2):398-411
references.pmid: 16472595
references.citation: Int J Cancer. 2008 May 15;122(10):2187-98
references.pmid: 18092325
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):194-202
references.pmid: 16492905
references.citation: Allergy Asthma Immunol Res. 2010 Jan;2(1):20-7
references.pmid: 20224674
references.citation: J Biol Chem. 1995 Jun 2;270(22):13076-83
references.pmid: 7768902
references.citation: Proc Assoc Am Physicians. 1998 Jul-Aug;110(4):351-60
references.pmid: 9686683
references.citation: BMC Cancer. 2010 Jun 16;10:295
references.pmid: 20553613
references.citation: Biochem J. 2004 Jun 15;380(Pt 3):651-9
references.pmid: 15015934