Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone

  • Authors:
    • Daisuke Tamura
    • Toru Hiraga
    • Akira Myoui
    • Hideki Yoshikawa
    • Toshiyuki Yoneda
  • Corresponding author:
  • View Affiliations

  • Published online on: Tuesday, July 1, 2008
  • Pages: 17-24 DOI: 10.3892/ijo.33.1.17

Abstract

Cell adhesion molecules have been implicated in the selective colonization of cancer in distant organs. Breast cancer has a strong predilection for spreading to bone. Cadherin-11, which is one of the classical type-2 cadherin family members and mediates homophilic cell-cell adhesion, is constitutively expressed in stromal and osteoblastic cells in bone marrow. Elevated cadherin-11 expression is also found in aggressive human breast cancers. Here, we investigated the role of the interactions between breast cancer cells and bone marrow stromal/osteoblastic cells via cadherin-11 in the selective spread to bone. The bone-seeking clone of the MDA-MB-231 human breast cancer cells showed greater cadherin-11 expression than the parental and the brain-seeking clone. Cadherin-11 overexpression in MDA-MB-231 cells increased bone metastases with promoted bone resorption, while the natural variant form of cadherin-11 that is unable to establish cell-cell adhesion did not. Of note, introduction of cadherin-11 showed no effects on lung metastases. Fluorescence-activated cell sorter analysis using the fluorescent dye-labeled cancer cells showed that early colonization in bone marrow was increased by cadherin-11. Co-cultures with the MC3T3-E1 osteoblastic cells that constitutively expressed cadherin-11 caused an up-regulation of parathyroid hormone-related protein (PTH-rP) production in MDA-MB-231 cells overexpressing cadherin-11. The conditioned medium of the co-cultures increased osteoclastogenesis, which was blocked by a neutralizing antibody to PTH-rP. In conclusion, our results suggest that cadherin-11 promotes homing and migration to bone and osteoclastogenesis through mediating the homophilic interactions of breast cancer cells with marrow stromal/osteoblastic cells, thereby enhancing bone metastases.
Journal Cover

July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
2014 I.F. (Expected) ≥ 3.258 Ranked #30/202 Oncology
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APA
Tamura, D., Hiraga, T., Myoui, A., Yoshikawa, H., & Yoneda, T. (2008). Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone. International Journal of Oncology, 33, 17-24. http://dx.doi.org/10.3892/ijo.33.1.17
MLA
Tamura, D., Hiraga, T., Myoui, A., Yoshikawa, H., Yoneda, T."Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone". International Journal of Oncology 33.1 (2008): 17-24.
Chicago
Tamura, D., Hiraga, T., Myoui, A., Yoshikawa, H., Yoneda, T."Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone". International Journal of Oncology 33, no. 1 (2008): 17-24. http://dx.doi.org/10.3892/ijo.33.1.17