title: Cadherin-11 in renal cell carcinoma bone metastasis.
abstract: Bone is one of the common sites of metastases from renal cell carcinoma (RCC), however the mechanism by which RCC preferentially metastasize to bone is poorly understood. Homing/retention of RCC cells to bone and subsequent proliferation are necessary steps for RCC cells to colonize bone. To explore possible mechanisms by which these processes occur, we used an in vivo metastasis model in which 786-O RCC cells were injected into SCID mice intracardially, and organotropic cell lines from bone, liver, and lymph node were selected. The expression of molecules affecting cell adhesion, angiogenesis, and osteolysis were then examined in these selected cells. Cadherin-11, a mesenchymal cadherin mainly expressed in osteoblasts, was significantly increased on the cell surface in bone metastasis-derived 786-O cells (Bo-786-O) compared to parental, liver, or lymph node-derived cells. In contrast, the homing receptor CXCR4 was equivalently expressed in cells derived from all organs. No significant difference was observed in the expression of angiogenic factors, including HIF-1α, VEGF, angiopoeitin-1, Tie2, c-MET, and osteolytic factors, including PTHrP, IL-6 and RANKL. While the parental and Bo-786-O cells have similar proliferation rates, Bo-786-O cells showed an increase in migration compared to the parental 786-O cells. Knockdown of Cadherin-11 using shRNA reduced the rate of migration in Bo-786-O cells, suggesting that Cadherin-11 contributes to the increased migration observed in bone-derived cells. Immunohistochemical analysis of cadherin-11 expression in a human renal carcinoma tissue array showed that the number of human specimens with positive cadherin-11 activity was significantly higher in tumors that metastasized to bone than that in primary tumors. Together, these results suggest that Cadherin-11 may play a role in RCC bone metastasis.
authors.affiliation: Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Satcher
authors.affiliation: Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Pan
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chien-Jui
authors.initials: CJ
authors.lastname: Cheng
authors.affiliation: Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Yu
authors.affiliation: Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Anh G
authors.initials: AG
authors.lastname: Hoang
authors.affiliation: Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.affiliation: Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Jonasch
authors.affiliation: Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gallick
authors.affiliation: Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America ; Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Sue-Hwa
authors.initials: SH
authors.lastname: Lin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000637:transplantation
chemical_list: C514936:CXCR4 protein, mouse; D015820:Cadherins; D019718:Receptors, CXCR4; C086960:osteoblast cadherin