Research Article Open Access

The Cell to Cell Interaction of Breast Cancer Cells Regulates Cancer Invasion Via ADAM15

Daichi Ota1, Masahiro Ikesue1, Yutaka Matsui1, Koyu Ito1, Yoshikazu Takada2, Ann F. Chambers3 and Toshimitsu Uede1
  • 1 Hokkaido University, Japan
  • 2 The University of California Davis Medical Center, United States
  • 3 The University of Western Ontario, Canada

Abstract

Increasing evidence suggests that a disintegrin and metalloproteinase 15 (ADAM15) have essential roles in the process of cancer metastasis via degradation of the extracellular matrix and binding to integrins. Among them, ADAM15 possesses an Arg-Gly-Asp (RGD) sequence within its disintegrin domain (d.d., hereafter) and binds to RGD recognizing-integrins such as αvβ3 and α5β1 and also interacts with integrin α9β1 in RGD-independent manner. Although these integrins play important roles in the process of cancer metastasis, the role of the interactions between ADAM15 and integrins during processes of cancer metastasis remains to be elucidated. We produced the specific antibody (8F7) that interferes with the interaction of human ADAM15 and integrin receptors and performed in vitro aggregation assay, invasion assay, proliferation assay, proteinase activity assay and cell-cell adhesion assay. 8F7 inhibited tumor cell aggregation, invasion and migration, but not proliferation of breast cancer cells and proteinase activity of ADAM15. Furthermore, the interactions between ADAM15 and integrin receptors induced collective cell migration, phosphorylation of Akt, which was known to promote invasion of breast cancer cells. These data suggested that the binding of ADAM15 to αvβ3 or α9β1 integrins through its d.d. Induces cell aggregation, migration and invasion of human breast cancer cells with concomitant activation of Akt signaling pathway.

American Journal of Immunology
Volume 8 No. 4, 2012, 123-135

DOI: https://doi.org/10.3844/ajisp.2012.123.135

Submitted On: 5 June 2012 Published On: 17 October 2012

How to Cite: Ota, D., Ikesue, M., Matsui, Y., Ito, K., Takada, Y., Chambers, A. F. & Uede, T. (2012). The Cell to Cell Interaction of Breast Cancer Cells Regulates Cancer Invasion Via ADAM15. American Journal of Immunology, 8(4), 123-135. https://doi.org/10.3844/ajisp.2012.123.135

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Keywords

  • ADAM15
  • Integrins
  • Cell to Cell Interaction
  • Cell Motility
  • Phosphorylation of Akt