Recombinant disintegrin domain of human ADAM9 inhibits migration and invasion of DU145 prostate tumor cells

重组人 ADAM9 解整合素结构域抑制 DU145 前列腺肿瘤细胞的迁移和侵袭

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作者:Ana Carolina Baptista Moreno Martin, Ana Carolina Ferreira Cardoso, Heloisa Sobreiro Selistre-de-Araujo, Márcia Regina Cominetti

Abstract

One of the most important features of malignant cells is their capacity to invade adjacent tissues and metastasize to distant organs. This process involves the creation, by tumor and stroma cells, of a specific microenvironment, suitable for proliferation, migration and invasion of tumor cells. The ADAM family of proteins has been involved in these processes. This work aimed to investigate the role of the recombinant disintegrin domain of the human ADAM9 (rADAM9D) on the adhesive and mobility properties of DU145 prostate tumor cells. rADAM9D was able to support DU145 cell adhesion, inhibit the migration of DU145 cells, as well as the invasion of this cell line through matrigel in vitro. Overall this work demonstrates that rADAM9D induces specific cellular migratory properties when compared with different constructs having additional domains, specially those of metalloproteinase and cysteine-rich domains. Furthermore, we showed that rADAM9D was able to inhibit cell adhesion, migration and invasion mainly through interacting with α6β1 in DU145 tumor cell line. These results may contribute to the development of new therapeutic strategies for prostate cancer.

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