Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Feb 24;9(2):e89880. doi: 10.1371/journal.pone.0089880. eCollection 2014.

Cadherin-11 in renal cell carcinoma bone metastasis.

Author information

  • 1Orthopedic Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
  • 2Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.
  • 3Translational Molecular Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
  • 4Genitourinary Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
  • 5Pathology, University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
  • 6Translational 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.

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.

PMID:
24587095
[PubMed - indexed for MEDLINE]
PMCID:
PMC3933681
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk