title: Inhibition of cell adhesion by a cadherin-11 antibody thwarts bone metastasis.
abstract: Cadherin-11 (CDH11) is a member of the cadherin superfamily mainly expressed in osteoblasts but not in epithelial cells. However, prostate cancer cells with a propensity for bone metastasis express high levels of cadherin-11 and reduced levels of E-cadherin. Downregulation of cadherin-11 inhibits interaction of prostate cancer cells with osteoblasts in vitro and homing of prostate cancer cells to bone in an animal model of metastasis. These findings indicate that targeting cadherin-11 may prevent prostate cancer bone metastasis. To explore this possibility, a panel of 21 monoclonal antibodies (mAb) was generated against the extracellular (EC) domain of cadherin-11. Two antibodies, mAbs 2C7 and 1A5, inhibited cadherin-11-mediated cell-cell aggregation in vitro using L-cells transfected with cadherin-11. Both antibodies demonstrated specificity to cadherin-11, and neither antibody recognized E-cadherin or N-cadherin on C4-2B or PC3 cells, respectively. Furthermore, mAb 2C7 inhibited cadherin-11-mediated aggregation between the highly metastatic PC3-mm2 cells and MC3T3-E1 osteoblasts. Mechanistically, a series of deletion mutants revealed a unique motif, aa 343-348, in the cadherin-11 EC3 domain that is recognized by mAb 2C7 and that this motif coordinated cell-cell adhesion. Importantly, administration of mAb 2C7 in a prophylactic setting effectively prevented metastasis of PC3-mm2 cells to bone in an in vivo mouse model. These results show that targeting the extracellular domain of cadherin-11 can limit cellular adhesion and metastatic dissemination of prostate cancer cells.
  
  
  CONCLUSIONS
  Monotherapy using a cadherin-11 antibody is a suitable option for the prevention of bone metastases.
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Mehmet Asim
authors.initials: MA
authors.lastname: Bilen
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Yu
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.|Department of Pharmacy at National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chih-Fen
authors.initials: CF
authors.lastname: Huang
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Angelica
authors.initials: A
authors.lastname: Ortiz
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Cho
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jian H
authors.initials: JH
authors.lastname: Song
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Satcher
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Jian
authors.initials: J
authors.lastname: Kuang
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gallick
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Li-Yuan
authors.initials: LY
authors.lastname: Yu-Lee
authors.affiliation: Abnova Corporation, Taiwan.
authors.forename: Wilber
authors.initials: W
authors.lastname: Huang
authors.affiliation: Departments of Translational Molecular Pathology, Genitourinary Medical Oncology, Orthopaedic Oncology, Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D002465:Cell Movement; D018604:Epitope Mapping; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D015820:Cadherins; C086960:osteoblast cadherin
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