Cadherin-11 in renal cell carcinoma bone metastasis

Robert L. Satcher, Tianhong Pan, Chien Jui Cheng, Yu Chen Lee, Song Chang Lin, Guoyu Yu, Xiaoxia Li, Anh G. Hoang, Pheroze Tamboli, Eric Jonasch, Gary E. Gallick, Sue Hwa Lin

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18 Citations (Scopus)

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.

Original languageEnglish
Article numbere89880
JournalPLoS One
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 24 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Satcher, R. L., Pan, T., Cheng, C. J., Lee, Y. C., Lin, S. C., Yu, G., Li, X., Hoang, A. G., Tamboli, P., Jonasch, E., Gallick, G. E., & Lin, S. H. (2014). Cadherin-11 in renal cell carcinoma bone metastasis. PLoS One, 9(2), [e89880]. https://doi.org/10.1371/journal.pone.0089880