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BioMed Research International
Volume 2014 (2014), Article ID 482396, 13 pages
Research Article

A Disintegrin and Metalloproteinase 9 Is Involved in Ectodomain Shedding of Receptor-Binding Cancer Antigen Expressed on SiSo Cells

Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan

Received 16 April 2014; Revised 16 June 2014; Accepted 9 July 2014; Published 7 August 2014

Academic Editor: Dominique Alfandari

Copyright © 2014 Kenzo Sonoda and Kiyoko Kato. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In several human malignancies, the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is associated with aggressive characteristics and poor overall survival. RCAS1 alters the tumor microenvironment by inducing peripheral lymphocyte apoptosis and angiogenesis, while reducing the vimentin-positive cell population. Although proteolytic processing, referred to as “ectodomain shedding,” is pivotal for induction of apoptosis by RCAS1, the proteases involved in RCAS1-dependent shedding remain unclear. Here we investigated proteases involved in RCAS1 shedding and the association between tumor protease expression and serum RCAS1 concentration in uterine cancer patients. A disintegrin and metalloproteinase (ADAM) 9 was shown to be involved in the ectodomain shedding of RCAS1. Given the significant correlation between tumor ADAM9 expression and serum RCAS1 concentration in both cervical and endometrial cancer as well as the role for ADAM9 in RCAS1 shedding, further exploration of the regulatory mechanisms by which ADAM9 converts membrane-anchored RCAS1 into its soluble form should aid the development of novel RCAS1-targeting therapeutic strategies to treat human malignancies.