The Cell to Cell Interaction of Breast Cancer Cells Regulates Cancer Invasion Via ADAM15
Daichi Ota, Masahiro Ikesue, Yutaka Matsui, Koyu Ito, Yoshikazu Takada, Ann F. Chambers and Toshimitsu Uede
DOI : 10.3844/ajisp.2012.123.135
American Journal of Immunology
Volume 8, 2012
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.
© 2012 Daichi Ota, Masahiro Ikesue, Yutaka Matsui, Koyu Ito, Yoshikazu Takada, Ann F. Chambers and Toshimitsu Uede. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.