TY - JOUR
T1 - The cell to cell interaction of breast cancer cells regulates cancer invasion via adam15
AU - Ota, Daichi
AU - Ikesue, Masahiro
AU - Matsui, Yutaka
AU - Ito, Koyu
AU - Takada, Yoshikazu
AU - Chambers, Ann F.
AU - Uede, Toshimitsu
PY - 2012/10/17
Y1 - 2012/10/17
N2 - 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 avb3 and a5b1 and also interacts with integrin a9b1 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 avb3 or a9b1 integrins through its d.d. Induces cell aggregation, migration and invasion of human breast cancer cells with concomitant activation of Akt signaling pathway.
AB - 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 avb3 and a5b1 and also interacts with integrin a9b1 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 avb3 or a9b1 integrins through its d.d. Induces cell aggregation, migration and invasion of human breast cancer cells with concomitant activation of Akt signaling pathway.
KW - ADAM15
KW - Cell motility
KW - Cell to cell interaction
KW - Integrins
KW - Phosphorylation of Akt
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U2 - 10.3844/ajisp.2012.123.135
DO - 10.3844/ajisp.2012.123.135
M3 - Article
AN - SCOPUS:84876860699
SN - 1553-619X
VL - 8
SP - 123
EP - 135
JO - American Journal of Immunology
JF - American Journal of Immunology
IS - 4
ER -